Carrel name: journal-frontImmunol-cord Creating study carrel named journal-frontImmunol-cord Initializing database file: cache/cord-003091-uvfppirt.json key: cord-003091-uvfppirt authors: Gornati, Laura; Zanoni, Ivan; Granucci, Francesca title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines date: 2018-06-27 journal: Front Immunol DOI: 10.3389/fimmu.2018.01484 sha: doc_id: 3091 cord_uid: uvfppirt file: cache/cord-001674-tp4o7fxx.json key: cord-001674-tp4o7fxx authors: Oliveira, Cláudia C.; van Hall, Thorbald title: Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome date: 2015-06-05 journal: Front Immunol DOI: 10.3389/fimmu.2015.00298 sha: doc_id: 1674 cord_uid: tp4o7fxx file: cache/cord-253108-p3wlw5d4.json key: cord-253108-p3wlw5d4 authors: Olson, Brian M.; Sullivan, Jeremy A.; Burlingham, William J. title: Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance date: 2013-10-18 journal: Front Immunol DOI: 10.3389/fimmu.2013.00315 sha: doc_id: 253108 cord_uid: p3wlw5d4 file: cache/cord-003319-u88gznxq.json key: cord-003319-u88gznxq authors: Huang, Weishan; Solouki, Sabrina; Carter, Chavez; Zheng, Song-Guo; August, Avery title: Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages date: 2018-11-19 journal: Front Immunol DOI: 10.3389/fimmu.2018.02625 sha: doc_id: 3319 cord_uid: u88gznxq file: cache/cord-003656-7mzsaz7a.json key: cord-003656-7mzsaz7a authors: Wium, Martha; Jonker, Hester Isabella; Olivier, Adriaan Jacobus; Bellstedt, Dirk Uwe; Botes, Annelise title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 journal: Front Immunol DOI: 10.3389/fimmu.2019.01061 sha: doc_id: 3656 cord_uid: 7mzsaz7a file: cache/cord-003378-0ozhye9q.json key: cord-003378-0ozhye9q authors: Yu, Haijing; Liu, Yang; Wang, Hongwu; Wan, Xiaoyang; Huang, Jiaquan; Yan, Weiming; Xi, Dong; Luo, Xiaoping; Shen, Guanxin; Ning, Qin title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression date: 2018-12-13 journal: Front Immunol DOI: 10.3389/fimmu.2018.02935 sha: doc_id: 3378 cord_uid: 0ozhye9q file: cache/cord-033488-du8heorx.json key: cord-033488-du8heorx authors: Ho, Thuong Thi; Nguyen, Giang Thu; Pham, Ngoc Bich; Le, Van Phan; Trinh, Thi Bich Ngoc; Vu, Trang Huyen; Phan, Hoang Trong; Conrad, Udo; Chu, Ha Hoang title: Plant-Derived Trimeric CO-26K-Equivalent Epitope Induced Neutralizing Antibodies Against Porcine Epidemic Diarrhea Virus date: 2020-09-16 journal: Front Immunol DOI: 10.3389/fimmu.2020.02152 sha: doc_id: 33488 cord_uid: du8heorx file: cache/cord-268781-6l74rrlm.json key: cord-268781-6l74rrlm authors: Poh, Chek Meng; Zheng, Jian; Channappanavar, Rudragouda; Chang, Zi Wei; Nguyen, Thi H. O.; Rénia, Laurent; Kedzierska, Katherine; Perlman, Stanley; Poon, Leo L. M. title: Multiplex Screening Assay for Identifying Cytotoxic CD8(+) T Cell Epitopes date: 2020-03-11 journal: Front Immunol DOI: 10.3389/fimmu.2020.00400 sha: doc_id: 268781 cord_uid: 6l74rrlm file: cache/cord-003545-corvd5cs.json key: cord-003545-corvd5cs authors: Li, Chen; Liu, Jiaxin; Zhang, Xin; Wei, Shina; Huang, Xiaohong; Huang, Youhua; Wei, Jingguang; Qin, Qiwei title: Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus date: 2019-03-19 journal: Front Immunol DOI: 10.3389/fimmu.2019.00517 sha: doc_id: 3545 cord_uid: corvd5cs file: cache/cord-003368-f8f2utzx.json key: cord-003368-f8f2utzx authors: Lutterberg, Karina; Kleinwort, Kristina J. H.; Hobmaier, Bernhard F.; Hauck, Stefanie M.; Nüske, Stefan; Scholz, Armin M.; Deeg, Cornelia A. title: A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence date: 2018-12-06 journal: Front Immunol DOI: 10.3389/fimmu.2018.02884 sha: doc_id: 3368 cord_uid: f8f2utzx file: cache/cord-004151-9815ikzg.json key: cord-004151-9815ikzg authors: Pan, Xiaocheng; Zhang, Nianzhi; Wei, Xiaohui; Jiang, Yinan; Chen, Rong; Li, Qirun; Liang, Ruiying; Zhang, Lijie; Ma, Lizhen; Xia, Chun title: Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) date: 2020-01-08 journal: Front Immunol DOI: 10.3389/fimmu.2019.02995 sha: doc_id: 4151 cord_uid: 9815ikzg file: cache/cord-030803-6i0e2zkd.json key: cord-030803-6i0e2zkd authors: Hu, Wan-Chung title: A Framework of All Discovered Immunological Pathways and Their Roles for Four Specific Types of Pathogens and Hypersensitivities date: 2020-08-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.01992 sha: doc_id: 30803 cord_uid: 6i0e2zkd file: cache/cord-257662-viy65y72.json key: cord-257662-viy65y72 authors: Burrack, Kristina S.; Morrison, Thomas E. title: The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases date: 2014-09-08 journal: Front Immunol DOI: 10.3389/fimmu.2014.00428 sha: doc_id: 257662 cord_uid: viy65y72 file: cache/cord-003122-a3f4l6iu.json key: cord-003122-a3f4l6iu authors: Dou, Dan; Revol, Rebecca; Östbye, Henrik; Wang, Hao; Daniels, Robert title: Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement date: 2018-07-20 journal: Front Immunol DOI: 10.3389/fimmu.2018.01581 sha: doc_id: 3122 cord_uid: a3f4l6iu file: cache/cord-265005-e6rpryrh.json key: cord-265005-e6rpryrh authors: Tomasello, Elena; Pollet, Emeline; Vu Manh, Thien-Phong; Uzé, Gilles; Dalod, Marc title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 journal: Front Immunol DOI: 10.3389/fimmu.2014.00526 sha: doc_id: 265005 cord_uid: e6rpryrh file: cache/cord-265855-zf52vl11.json key: cord-265855-zf52vl11 authors: Mayor-Ibarguren, Ander; 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Celer, Vladimir; Kavanová, Lenka; Levá, Lenka; Frolichova, Jitka; Ondráčková, Petra; Kudláčková, Hana; Nechvátalová, Kateřina; Salat, Jiri; Faldyna, Martin title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus date: 2019-08-06 journal: Front Immunol DOI: 10.3389/fimmu.2019.01689 sha: doc_id: 3825 cord_uid: tkqxb1ql file: cache/cord-261367-i1n8x0uc.json key: cord-261367-i1n8x0uc authors: Hwang, Ji Young; Silva-Sanchez, Aaron; Carragher, Damian M.; Garcia-Hernandez, Maria de la Luz; Rangel–Moreno, Javier; Randall, Troy D. title: Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date: 2020-09-25 journal: Front Immunol DOI: 10.3389/fimmu.2020.570661 sha: doc_id: 261367 cord_uid: i1n8x0uc file: cache/cord-034310-izpt032p.json key: cord-034310-izpt032p authors: Chernomordik, Fernando; Cercek, Bojan; Lio, Wai Man; Mihailovic, Peter M.; Yano, Juliana; Herscovici, Romana; Zhao, Xiaoning; Zhou, Jianchang; Chyu, Kuang-Yuh; Shah, Prediman K.; Dimayuga, Paul C. title: The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification date: 2020-10-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.575577 sha: doc_id: 34310 cord_uid: izpt032p file: cache/cord-267134-5gz2dotn.json key: cord-267134-5gz2dotn authors: Sallenave, Jean-Michel; Guillot, Loïc title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date: 2020-05-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.01229 sha: doc_id: 267134 cord_uid: 5gz2dotn file: cache/cord-267567-w39f584z.json key: cord-267567-w39f584z authors: Pombo, Joao Palma; Sanyal, Sumana title: Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections date: 2018-06-04 journal: Front Immunol DOI: 10.3389/fimmu.2018.01276 sha: doc_id: 267567 cord_uid: w39f584z file: cache/cord-284867-p4jgyusp.json key: cord-284867-p4jgyusp authors: Schöler, Lara; Le-Trilling, Vu Thuy Khanh; Eilbrecht, Mareike; Mennerich, Denise; Anastasiou, Olympia E.; Krawczyk, Adalbert; Herrmann, Anke; Dittmer, Ulf; Trilling, Mirko title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 journal: Front Immunol DOI: 10.3389/fimmu.2020.573526 sha: doc_id: 284867 cord_uid: p4jgyusp file: cache/cord-000647-uofygmeu.json key: cord-000647-uofygmeu authors: Stäger, Simona; Rafati, Sima title: CD8(+) T Cells in Leishmania Infections: Friends or Foes? date: 2012-01-24 journal: Front Immunol DOI: 10.3389/fimmu.2012.00005 sha: doc_id: 647 cord_uid: uofygmeu file: cache/cord-015254-xtox2rxs.json key: cord-015254-xtox2rxs authors: Li, Hao-Ling; Huang, Yan; Zhou, Ya-Lan; Teng, Run-Hua; Zhou, Shu-Zhuan; Lin, Jia-Piao; Yang, Yan; Zhu, Sheng-Mei; Xu, Hua; Yao, Yong-Xing title: C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood–Spinal Cord Barrier date: 2020-03-20 journal: Front Immunol DOI: 10.3389/fimmu.2020.00477 sha: doc_id: 15254 cord_uid: xtox2rxs file: cache/cord-268501-z4oztgi0.json key: cord-268501-z4oztgi0 authors: Palatnik-de-Sousa, Clarisa B. title: What Would Jenner and Pasteur Have Done About COVID-19 Coronavirus? The Urges of a Vaccinologist date: 2020-08-26 journal: Front Immunol DOI: 10.3389/fimmu.2020.02173 sha: doc_id: 268501 cord_uid: z4oztgi0 file: cache/cord-268438-bjs5oliw.json key: cord-268438-bjs5oliw authors: Jin, Yilin; Jia, Kuntong; Zhang, Wanwan; Xiang, Yangxi; Jia, Peng; Liu, Wei; Yi, Meisheng title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination date: 2019-12-03 journal: Front Immunol DOI: 10.3389/fimmu.2019.02805 sha: doc_id: 268438 cord_uid: bjs5oliw file: cache/cord-003914-ss8vdpox.json key: cord-003914-ss8vdpox authors: Wang, Shenghua; Geng, Na; Zhou, Dong; Qu, Yi; Shi, Mengke; Xu, Yuliang; Liu, Kangping; Liu, Yongxia; Liu, Jianzhu title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection date: 2019-10-02 journal: Front Immunol DOI: 10.3389/fimmu.2019.02299 sha: doc_id: 3914 cord_uid: ss8vdpox file: cache/cord-262575-06i2nv0t.json key: cord-262575-06i2nv0t authors: Caracciolo, Massimo; Macheda, Sebastiano; Labate, Demetrio; Tescione, Marco; La Scala, Stefano; Vadalà, Eugenio; Squillaci, Rosalba; D’Aleo, Francesco; Morabito, Antonella; Garreffa, Cristina; Marciano, Maria Concetta; Oliva, Esther N. title: Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome date: 2020-08-25 journal: Front Immunol DOI: 10.3389/fimmu.2020.01942 sha: doc_id: 262575 cord_uid: 06i2nv0t file: cache/cord-259131-36udb7uc.json key: cord-259131-36udb7uc authors: Hunegnaw, Ruth; Mushtaq, Zuena; Enyindah-Asonye, Gospel; Hoang, Tanya; Robert-Guroff, Marjorie title: Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques date: 2019-07-03 journal: Front Immunol DOI: 10.3389/fimmu.2019.01537 sha: doc_id: 259131 cord_uid: 36udb7uc file: cache/cord-262673-j2ot35lt.json key: cord-262673-j2ot35lt authors: Ahmed-Hassan, Hanaa; Sisson, Brianna; Shukla, Rajni Kant; Wijewantha, Yasasvi; Funderburg, Nicholas T.; Li, Zihai; Hayes, Don; Demberg, Thorsten; Liyanage, Namal P. M. title: Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections date: 2020-08-18 journal: Front Immunol DOI: 10.3389/fimmu.2020.01979 sha: doc_id: 262673 cord_uid: j2ot35lt file: cache/cord-282336-zvc04s39.json key: cord-282336-zvc04s39 authors: Choudhary, Ishita; Vo, Thao; Bathula, Chandra S.; Lamichhane, Richa; Lewis, Brandon W.; Looper, Jayme; Jeyaseelan, Samithamby; Blackshear, Perry J.; Saini, Yogesh; Patial, Sonika title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 journal: Front Immunol DOI: 10.3389/fimmu.2020.02164 sha: doc_id: 282336 cord_uid: zvc04s39 file: cache/cord-255578-0ltb9dpa.json key: cord-255578-0ltb9dpa authors: Li, Xiangru; Hao, Zhenhua; Liu, Xiaorong; Li, Wei title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 journal: Front Immunol DOI: 10.3389/fimmu.2020.01123 sha: doc_id: 255578 cord_uid: 0ltb9dpa file: cache/cord-257116-6td3efjw.json key: cord-257116-6td3efjw authors: Zhou, Yanrong; Wu, Wei; Xie, Lilan; Wang, Dang; Ke, Qiyun; Hou, Zhenzhen; Wu, Xiaoli; Fang, Ying; Chen, Huanchun; Xiao, Shaobo; Fang, Liurong title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production date: 2017-08-09 journal: Front Immunol DOI: 10.3389/fimmu.2017.00940 sha: doc_id: 257116 cord_uid: 6td3efjw file: cache/cord-262375-1ex2ow07.json key: cord-262375-1ex2ow07 authors: Qun, Sen; Wang, Yulan; Chen, Jun; Huang, Xiang; Guo, Hui; Lu, Zhaohui; Wang, Jinquan; Zheng, Changcheng; Ma, Yan; Zhu, Yuyou; Xia, Daqing; Wang, Yinzhong; He, Hongliang; Wang, Yong; Fei, Mingming; Yin, Yihong; Zheng, Mao; Xu, Yehong; Ge, Wei; Hu, Fuyong; Zhou, Jian title: Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19 date: 2020-09-02 journal: Front Immunol DOI: 10.3389/fimmu.2020.02160 sha: doc_id: 262375 cord_uid: 1ex2ow07 file: cache/cord-284156-btb4oodz.json key: cord-284156-btb4oodz authors: Liu, Yiliu; Olagnier, David; Lin, Rongtuan title: Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity date: 2017-01-03 journal: Front Immunol DOI: 10.3389/fimmu.2016.00662 sha: doc_id: 284156 cord_uid: btb4oodz file: cache/cord-298458-p7rvupjo.json key: cord-298458-p7rvupjo authors: Schmidt, Megan E.; Varga, Steven M. title: The CD8 T Cell Response to Respiratory Virus Infections date: 2018-04-09 journal: Front Immunol DOI: 10.3389/fimmu.2018.00678 sha: doc_id: 298458 cord_uid: p7rvupjo file: cache/cord-030385-btf502ju.json key: cord-030385-btf502ju authors: Sun, Zhiheng; Pan, Yuchen; Qu, Junxing; Xu, Yujun; Dou, Huan; Hou, Yayi title: 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date: 2020-07-22 journal: Front Immunol DOI: 10.3389/fimmu.2020.01591 sha: doc_id: 30385 cord_uid: btf502ju file: cache/cord-032953-qy4b2l2f.json key: cord-032953-qy4b2l2f authors: Picard-Sánchez, Amparo; Estensoro, Itziar; Perdiguero, Pedro; del Pozo, Raquel; Tafalla, Carolina; Piazzon, M. Carla; Sitjà-Bobadilla, Ariadna title: Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire date: 2020-09-11 journal: Front Immunol DOI: 10.3389/fimmu.2020.581361 sha: doc_id: 32953 cord_uid: qy4b2l2f file: cache/cord-262944-9k64f0tw.json key: cord-262944-9k64f0tw authors: Parker, Elaine L.; Silverstein, Rachel B.; Verma, Sonam; Mysorekar, Indira U. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.522047 sha: doc_id: 262944 cord_uid: 9k64f0tw file: cache/cord-298604-tn8hc6jv.json key: cord-298604-tn8hc6jv authors: Khawaja, Akif A.; Chong, Deborah L. W.; Sahota, Jagdeep; Mikolasch, Theresia A.; Pericleous, Charis; Ripoll, Vera M.; Booth, Helen L.; Khan, Saif; Rodriguez-Justo, Manuel; Giles, Ian P.; Porter, Joanna C. title: Identification of a Novel HIF-1α-α(M)β(2) Integrin-NET Axis in Fibrotic Interstitial Lung Disease date: 2020-10-15 journal: Front Immunol DOI: 10.3389/fimmu.2020.02190 sha: doc_id: 298604 cord_uid: tn8hc6jv file: cache/cord-004477-qu2o2iu1.json key: cord-004477-qu2o2iu1 authors: Vlasova, Anastasia N.; Butler, John E. title: Editorial: Porcine Anti-Viral Immunity date: 2020-03-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.00399 sha: doc_id: 4477 cord_uid: qu2o2iu1 file: cache/cord-267237-wbwlfx7q.json key: cord-267237-wbwlfx7q authors: Gómez-Rial, Jose; Currás-Tuala, Maria José; Rivero-Calle, Irene; Gómez-Carballa, Alberto; Cebey-López, Miriam; Rodríguez-Tenreiro, Carmen; Dacosta-Urbieta, Ana; Rivero-Velasco, Carmen; Rodríguez-Núñez, Nuria; Trastoy-Pena, Rocio; Rodríguez-García, Javier; Salas, Antonio; Martinón-Torres, Federico title: Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology date: 2020-09-23 journal: Front Immunol DOI: 10.3389/fimmu.2020.560381 sha: doc_id: 267237 cord_uid: wbwlfx7q file: cache/cord-279105-e2zjxjox.json key: cord-279105-e2zjxjox authors: Lee, Cheryl Yi-Pin; Lin, Raymond T. P.; Renia, Laurent; Ng, Lisa F. P. title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 journal: Front Immunol DOI: 10.3389/fimmu.2020.00879 sha: doc_id: 279105 cord_uid: e2zjxjox file: cache/cord-288496-7rrh2gg6.json key: cord-288496-7rrh2gg6 authors: Stryhn, Anette; Kongsgaard, Michael; Rasmussen, Michael; Harndahl, Mikkel Nors; Østerbye, Thomas; Bassi, Maria Rosaria; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Nielsen, Morten; Christensen, Jan Pravsgaard; Randrup Thomsen, Allan; Buus, Soren title: A Systematic, Unbiased Mapping of CD8(+) and CD4(+) T Cell Epitopes in Yellow Fever Vaccinees date: 2020-08-31 journal: Front Immunol DOI: 10.3389/fimmu.2020.01836 sha: doc_id: 288496 cord_uid: 7rrh2gg6 file: cache/cord-020770-wpub7krf.json key: cord-020770-wpub7krf authors: Benmamar-Badel, Anouk; Owens, Trevor; Wlodarczyk, Agnieszka title: Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies date: 2020-04-03 journal: Front Immunol DOI: 10.3389/fimmu.2020.00430 sha: doc_id: 20770 cord_uid: wpub7krf file: cache/cord-252568-b8sbvy0g.json key: cord-252568-b8sbvy0g authors: Marques Neto, Lázaro Moreira; Kipnis, André; Junqueira-Kipnis, Ana Paula title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date: 2017-03-08 journal: Front Immunol DOI: 10.3389/fimmu.2017.00239 sha: doc_id: 252568 cord_uid: b8sbvy0g file: cache/cord-003685-jcvrqeew.json key: cord-003685-jcvrqeew authors: Gelain, Maria Elena; Bonsembiante, Federico title: Acute Phase Proteins in Marine Mammals: State of Art, Perspectives and Challenges date: 2019-05-29 journal: Front Immunol DOI: 10.3389/fimmu.2019.01220 sha: doc_id: 3685 cord_uid: jcvrqeew file: cache/cord-280924-g6062fwk.json key: cord-280924-g6062fwk authors: Hachim, Mahmood Yaseen; Al Heialy, Saba; Hachim, Ibrahim Yaseen; Halwani, Rabih; Senok, Abiola C.; Maghazachi, Azzam A.; Hamid, Qutayba title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date: 2020-06-10 journal: Front Immunol DOI: 10.3389/fimmu.2020.01372 sha: doc_id: 280924 cord_uid: g6062fwk file: cache/cord-297790-tpjxt0w5.json key: cord-297790-tpjxt0w5 authors: Mandl, Judith N.; Schneider, Caitlin; Schneider, David S.; Baker, Michelle L. title: Going to Bat(s) for Studies of Disease Tolerance date: 2018-09-20 journal: Front Immunol DOI: 10.3389/fimmu.2018.02112 sha: doc_id: 297790 cord_uid: tpjxt0w5 file: cache/cord-268483-joiajgs4.json key: cord-268483-joiajgs4 authors: Shah, Vibhuti Kumar; Firmal, Priyanka; Alam, Aftab; Ganguly, Dipyaman; Chattopadhyay, Samit title: Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date: 2020-08-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.01949 sha: doc_id: 268483 cord_uid: joiajgs4 file: cache/cord-003724-705h5l06.json key: cord-003724-705h5l06 authors: Di Lullo, Giulia; Calabresi, Valentina; Mariotti, Feliciana; Zambruno, Giovanna; Lanzavecchia, Antonio; Di Zenzo, Giovanni title: Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris date: 2019-06-19 journal: Front Immunol DOI: 10.3389/fimmu.2019.01391 sha: doc_id: 3724 cord_uid: 705h5l06 file: cache/cord-254192-86ksgl5t.json key: cord-254192-86ksgl5t authors: Li, Liang; Xue, Mei; Fu, Fang; Yin, Lingdan; Feng, Li; Liu, Pinghuang title: IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia date: 2019-10-17 journal: Front Immunol DOI: 10.3389/fimmu.2019.02394 sha: doc_id: 254192 cord_uid: 86ksgl5t file: cache/cord-254809-o454k6ae.json key: cord-254809-o454k6ae authors: He, Bing; Wang, Jun; Wang, Yudie; Zhao, Juan; Huang, Juan; Tian, Yu; Yang, Cheng; Zhang, Heng; Zhang, Mingxia; Gu, Lixing; Zhou, Xiaocui; Zhou, Jingjiao title: The Metabolic Changes and Immune Profiles in Patients With COVID-19 date: 2020-08-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.02075 sha: doc_id: 254809 cord_uid: o454k6ae file: cache/cord-269170-9f460xbq.json key: cord-269170-9f460xbq authors: Kaneko, Kazunari; Akagawa, Shohei; Akagawa, Yuko; Kimata, Takahisa; Tsuji, Shoji title: Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota date: 2020-07-24 journal: Front Immunol DOI: 10.3389/fimmu.2020.01616 sha: doc_id: 269170 cord_uid: 9f460xbq file: cache/cord-256998-or73in8m.json key: cord-256998-or73in8m authors: Nguyen, Khue G.; 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Magarian title: Sensing Microbial RNA in the Cytosol date: 2013-12-25 journal: Front Immunol DOI: 10.3389/fimmu.2013.00468 sha: doc_id: 323756 cord_uid: atnrw9ew file: cache/cord-328003-yovp8squ.json key: cord-328003-yovp8squ authors: Duan, Liangwei; Zheng, Qianqian; Zhang, Hongxia; Niu, Yuna; Lou, Yunwei; Wang, Hui title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.576622 sha: doc_id: 328003 cord_uid: yovp8squ file: cache/cord-340228-mvqoyror.json key: cord-340228-mvqoyror authors: Al-Herz, Waleed; Essa, Sahar title: Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry date: 2019-05-29 journal: Front Immunol DOI: 10.3389/fimmu.2019.01231 sha: doc_id: 340228 cord_uid: mvqoyror file: cache/cord-328011-6lf3no6u.json key: cord-328011-6lf3no6u authors: Zayed, Hatem title: Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics date: 2020-08-14 journal: Front Immunol DOI: 10.3389/fimmu.2020.02051 sha: doc_id: 328011 cord_uid: 6lf3no6u file: cache/cord-325353-tx6s4ggu.json key: cord-325353-tx6s4ggu authors: Restori, Katherine H.; Srinivasa, Bharat T.; Ward, Brian J.; Fixman, Elizabeth D. title: Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma date: 2018-06-04 journal: Front Immunol DOI: 10.3389/fimmu.2018.01249 sha: doc_id: 325353 cord_uid: tx6s4ggu file: cache/cord-328549-r56lih8j.json key: cord-328549-r56lih8j authors: Okamoto, Masaaki; Kouwaki, Takahisa; Fukushima, Yoshimi; Oshiumi, Hiroyuki title: Regulation of RIG-I Activation by K63-Linked Polyubiquitination date: 2018-01-05 journal: Front Immunol DOI: 10.3389/fimmu.2017.01942 sha: doc_id: 328549 cord_uid: r56lih8j file: cache/cord-318630-h6j7iqbm.json key: cord-318630-h6j7iqbm authors: Sinha, Sushmita; Boyden, Alexander W.; Itani, Farah R.; Crawford, Michael P.; Karandikar, Nitin J. title: CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis date: 2015-12-10 journal: Front Immunol DOI: 10.3389/fimmu.2015.00619 sha: doc_id: 318630 cord_uid: h6j7iqbm file: cache/cord-338261-tyimwctm.json key: cord-338261-tyimwctm authors: Farr, Laura; Ghosh, Swagata; Moonah, Shannon title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair date: 2020-06-23 journal: Front Immunol DOI: 10.3389/fimmu.2020.01273 sha: doc_id: 338261 cord_uid: tyimwctm file: cache/cord-338498-3238fz73.json key: cord-338498-3238fz73 authors: Kleen, Thomas-Oliver; Galdon, Alicia A.; MacDonald, Andrew S.; Dalgleish, Angus G. title: Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends” date: 2020-09-04 journal: Front Immunol DOI: 10.3389/fimmu.2020.02059 sha: doc_id: 338498 cord_uid: 3238fz73 file: cache/cord-348283-7xorq5ce.json key: cord-348283-7xorq5ce authors: Naz, Anam; Shahid, Fatima; Butt, Tariq Tahir; Awan, Faryal Mehwish; Ali, Amjad; Malik, Arif title: Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach date: 2020-07-10 journal: Front Immunol DOI: 10.3389/fimmu.2020.01663 sha: doc_id: 348283 cord_uid: 7xorq5ce file: cache/cord-351305-6vtv2xuh.json key: cord-351305-6vtv2xuh authors: Schramm, Markus A.; Venhoff, Nils; Wagner, Dirk; Thiel, Jens; Huzly, Daniela; Craig-Mueller, Nils; Panning, Marcus; Hengel, Hartmut; Kern, Winfried V.; Voll, Reinhard E. title: COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis date: 2020-08-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.02086 sha: doc_id: 351305 cord_uid: 6vtv2xuh file: cache/cord-344610-mqq6fmsp.json key: cord-344610-mqq6fmsp authors: Waumans, Yannick; Baerts, Lesley; Kehoe, Kaat; Lambeir, Anne-Marie; De Meester, Ingrid title: The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis date: 2015-08-07 journal: Front Immunol DOI: 10.3389/fimmu.2015.00387 sha: doc_id: 344610 cord_uid: mqq6fmsp file: cache/cord-350492-1s6wtj25.json key: cord-350492-1s6wtj25 authors: Ruscitti, Piero; Berardicurti, Onorina; Di Benedetto, Paola; Cipriani, Paola; Iagnocco, Annamaria; Shoenfeld, Yehuda; Giacomelli, Roberto title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm date: 2020-05-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.01130 sha: doc_id: 350492 cord_uid: 1s6wtj25 file: cache/cord-340475-h0q1m3ed.json key: cord-340475-h0q1m3ed authors: Carnero, Elena; Barriocanal, Marina; Segura, Victor; Guruceaga, Elizabeth; Prior, Celia; Börner, Kathleen; Grimm, Dirk; Fortes, Puri title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs date: 2014-11-06 journal: Front Immunol DOI: 10.3389/fimmu.2014.00548 sha: doc_id: 340475 cord_uid: h0q1m3ed file: cache/cord-344829-adlp2rjy.json key: cord-344829-adlp2rjy authors: de Rivero Vaccari, Juan Carlos; Dietrich, W. Dalton; Keane, Robert W.; de Rivero Vaccari, Juan Pablo title: The Inflammasome in Times of COVID-19 date: 2020-10-08 journal: Front Immunol DOI: 10.3389/fimmu.2020.583373 sha: doc_id: 344829 cord_uid: adlp2rjy file: cache/cord-336924-7xcbtn3q.json key: cord-336924-7xcbtn3q authors: Borghi, Maria Orietta; Beltagy, Asmaa; Garrafa, Emirena; Curreli, Daniele; Cecchini, Germana; Bodio, Caterina; Grossi, Claudia; Blengino, Simonetta; Tincani, Angela; Franceschini, Franco; Andreoli, Laura; Lazzaroni, Maria Grazia; Piantoni, Silvia; Masneri, Stefania; Crisafulli, Francesca; Brugnoni, Duilio; Muiesan, Maria Lorenza; Salvetti, Massimo; Parati, Gianfranco; Torresani, Erminio; Mahler, Michael; Heilbron, Francesca; Pregnolato, Francesca; Pengo, Martino; Tedesco, Francesco; Pozzi, Nicola; Meroni, Pier Luigi title: Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome date: 2020-10-15 journal: Front Immunol DOI: 10.3389/fimmu.2020.584241 sha: doc_id: 336924 cord_uid: 7xcbtn3q file: cache/cord-330417-8nnobx8g.json key: cord-330417-8nnobx8g authors: Herrmann, Marissa; Schulte, Sophia; Wildner, Nils H.; Wittner, Melanie; Brehm, Thomas Theo; Ramharter, Michael; Woost, Robin; Lohse, Ansgar W.; Jacobs, Thomas; Schulze zur Wiesch, Julian title: Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease date: 2020-08-26 journal: Front Immunol DOI: 10.3389/fimmu.2020.01870 sha: doc_id: 330417 cord_uid: 8nnobx8g file: cache/cord-353217-gmc3qrci.json key: cord-353217-gmc3qrci authors: de Miranda Santos, Isabel Kinney Ferreira; Costa, Carlos Henrique Nery title: Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus date: 2020-08-04 journal: Front Immunol DOI: 10.3389/fimmu.2020.01739 sha: doc_id: 353217 cord_uid: gmc3qrci file: cache/cord-341513-e6p3lrlf.json key: cord-341513-e6p3lrlf authors: Li, Yunchuan; Zhang, Hao; Zhu, Bibo; Ashraf, Usama; Chen, Zheng; Xu, Qiuping; Zhou, Dengyuan; Zheng, Bohan; Song, Yunfeng; Chen, Huanchun; Ye, Jing; Cao, Shengbo title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection date: 2017-09-29 journal: Front Immunol DOI: 10.3389/fimmu.2017.01237 sha: doc_id: 341513 cord_uid: e6p3lrlf file: cache/cord-342776-hkjhqgie.json key: cord-342776-hkjhqgie authors: Jewett, Anahid title: The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions date: 2020-07-10 journal: Front Immunol DOI: 10.3389/fimmu.2020.01692 sha: doc_id: 342776 cord_uid: hkjhqgie file: cache/cord-320663-xypg6evo.json key: cord-320663-xypg6evo authors: Market, Marisa; Angka, Leonard; Martel, Andre B.; Bastin, Donald; Olanubi, Oladunni; Tennakoon, Gayashan; Boucher, Dominique M.; Ng, Juliana; Ardolino, Michele; Auer, Rebecca C. title: Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies date: 2020-06-23 journal: Front Immunol DOI: 10.3389/fimmu.2020.01512 sha: doc_id: 320663 cord_uid: xypg6evo file: cache/cord-333041-69n2wwn3.json key: cord-333041-69n2wwn3 authors: Pal, Anandita; Gowdy, Kymberly M.; Oestreich, Kenneth J.; Beck, Melinda; Shaikh, Saame Raza title: Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection date: 2020-08-11 journal: Front Immunol DOI: 10.3389/fimmu.2020.01997 sha: doc_id: 333041 cord_uid: 69n2wwn3 file: cache/cord-325129-faptufak.json key: cord-325129-faptufak authors: Meini, Simone; Zanichelli, Andrea; Sbrojavacca, Rodolfo; Iuri, Federico; Roberts, Anna Teresa; Suffritti, Chiara; Tascini, Carlo title: Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key? date: 2020-08-11 journal: Front Immunol DOI: 10.3389/fimmu.2020.02014 sha: doc_id: 325129 cord_uid: faptufak file: cache/cord-334564-bqh9jkds.json key: cord-334564-bqh9jkds authors: Raony, Ícaro; de Figueiredo, Camila Saggioro; Pandolfo, Pablo; Giestal-de-Araujo, Elizabeth; Oliveira-Silva Bomfim, Priscilla; Savino, Wilson title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date: 2020-05-27 journal: Front Immunol DOI: 10.3389/fimmu.2020.01170 sha: doc_id: 334564 cord_uid: bqh9jkds file: cache/cord-323590-m4jsu1q5.json key: cord-323590-m4jsu1q5 authors: Ortiz de Landazuri, Iñaki; Egri, Natalia; Muñoz-Sánchez, Guillermo; Ortiz-Maldonado, Valentín; Bolaño, Victor; Guijarro, Carla; Pascal, Mariona; Juan, Manel title: Manufacturing and Management of CAR T-Cell Therapy in “COVID-19’s Time”: Central Versus Point of Care Proposals date: 2020-10-15 journal: Front Immunol DOI: 10.3389/fimmu.2020.573179 sha: doc_id: 323590 cord_uid: m4jsu1q5 file: cache/cord-353594-z1vxamvp.json key: cord-353594-z1vxamvp authors: Gagiannis, Daniel; Steinestel, Julie; Hackenbroch, Carsten; Schreiner, Benno; Hannemann, Michael; Bloch, Wilhelm; Umathum, Vincent G.; Gebauer, Niklas; Rother, Conn; Stahl, Marcel; Witte, Hanno M.; Steinestel, Konrad title: Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) date: 2020-10-02 journal: Front Immunol DOI: 10.3389/fimmu.2020.587517 sha: doc_id: 353594 cord_uid: z1vxamvp file: cache/cord-320474-jyk7zphp.json key: cord-320474-jyk7zphp authors: Bonaventura, Aldo; Vecchié, Alessandra; Wang, Tisha S.; Lee, Elinor; Cremer, Paul C.; Carey, Brenna; Rajendram, Prabalini; Hudock, Kristin M.; Korbee, Leslie; Van Tassell, Benjamin W.; Dagna, Lorenzo; Abbate, Antonio title: Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies date: 2020-07-03 journal: Front Immunol DOI: 10.3389/fimmu.2020.01625 sha: doc_id: 320474 cord_uid: jyk7zphp file: cache/cord-344093-3bniy5b5.json key: cord-344093-3bniy5b5 authors: Peteranderl, Christin; Herold, Susanne title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 journal: Front Immunol DOI: 10.3389/fimmu.2017.00313 sha: doc_id: 344093 cord_uid: 3bniy5b5 file: cache/cord-352960-pfccsgco.json key: cord-352960-pfccsgco authors: Gössling, Katharina L.; Schipp, Cyrill; Fischer, Ute; Babor, Florian; Koch, Gerhard; Schuster, Friedhelm R.; Dietzel-Dahmen, Jutta; Wieczorek, Dagmar; Borkhardt, Arndt; Meisel, Roland; Kuhlen, Michaela title: Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome date: 2017-06-30 journal: Front Immunol DOI: 10.3389/fimmu.2017.00773 sha: doc_id: 352960 cord_uid: pfccsgco file: cache/cord-338092-barmkkwx.json key: cord-338092-barmkkwx authors: Geginat, Jens; Nizzoli, Giulia; Paroni, Moira; Maglie, Stefano; Larghi, Paola; Pascolo, Steve; Abrignani, Sergio title: Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets date: 2015-10-13 journal: Front Immunol DOI: 10.3389/fimmu.2015.00527 sha: doc_id: 338092 cord_uid: barmkkwx file: cache/cord-340741-bhxm4zua.json key: cord-340741-bhxm4zua authors: Nayak, Tapas Kumar; Mamidi, Prabhudutta; Sahoo, Subhransu Sekhar; Kumar, P. Sanjai; Mahish, Chandan; Chatterjee, Sanchari; Subudhi, Bharat Bhusan; Chattopadhyay, Soma; Chattopadhyay, Subhasis title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 journal: Front Immunol DOI: 10.3389/fimmu.2019.00786 sha: doc_id: 340741 cord_uid: bhxm4zua file: cache/cord-350041-b1vmnwv2.json key: cord-350041-b1vmnwv2 authors: Cena, Hellas; Chieppa, Marcello title: Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection? date: 2020-05-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.00944 sha: doc_id: 350041 cord_uid: b1vmnwv2 file: cache/cord-354353-hyz0gmpz.json key: cord-354353-hyz0gmpz authors: Farhangrazi, Z. Shadi; Sancini, Giulio; Hunter, A. Christy; Moghimi, Seyed Moein title: Airborne Particulate Matter and SARS-CoV-2 Partnership: Virus Hitchhiking, Stabilization and Immune Cell Targeting — A Hypothesis date: 2020-09-24 journal: Front Immunol DOI: 10.3389/fimmu.2020.579352 sha: doc_id: 354353 cord_uid: hyz0gmpz file: cache/cord-351431-xcqz9d3t.json key: cord-351431-xcqz9d3t authors: Wang, Jun; Li, Qian; Yin, Yongmei; Zhang, Yingying; Cao, Yingying; Lin, Xiaoming; Huang, Lihua; Hoffmann, Daniel; Lu, Mengji; Qiu, Yuanwang title: Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19 date: 2020-08-18 journal: Front Immunol DOI: 10.3389/fimmu.2020.02063 sha: doc_id: 351431 cord_uid: xcqz9d3t file: cache/cord-353887-f4yd7guj.json key: cord-353887-f4yd7guj authors: Tang, Yujun; Liu, Jiajia; Zhang, Dingyi; Xu, Zhenghao; Ji, Jinjun; Wen, Chengping title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date: 2020-07-10 journal: Front Immunol DOI: 10.3389/fimmu.2020.01708 sha: doc_id: 353887 cord_uid: f4yd7guj file: cache/cord-346389-gbmnoo84.json key: cord-346389-gbmnoo84 authors: Callender, Lauren A.; Curran, Michelle; Bates, Stephanie M.; Mairesse, Maelle; Weigandt, Julia; Betts, Catherine J. title: The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19 date: 2020-08-11 journal: Front Immunol DOI: 10.3389/fimmu.2020.01991 sha: doc_id: 346389 cord_uid: gbmnoo84 file: cache/cord-350836-1enteev7.json key: cord-350836-1enteev7 authors: Brisse, Morgan; Ly, Hinh title: Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5 date: 2019-07-17 journal: Front Immunol DOI: 10.3389/fimmu.2019.01586 sha: doc_id: 350836 cord_uid: 1enteev7 file: cache/cord-336201-fl606l3b.json key: cord-336201-fl606l3b authors: Daryabor, Gholamreza; Atashzar, Mohamad Reza; Kabelitz, Dieter; Meri, Seppo; Kalantar, Kurosh title: The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System date: 2020-07-22 journal: Front Immunol DOI: 10.3389/fimmu.2020.01582 sha: doc_id: 336201 cord_uid: fl606l3b file: cache/cord-328763-hcbs20a0.json key: cord-328763-hcbs20a0 authors: Ifergan, Igal; Miller, Stephen D. title: Potential for Targeting Myeloid Cells in Controlling CNS Inflammation date: 2020-10-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.571897 sha: doc_id: 328763 cord_uid: hcbs20a0 file: cache/cord-354620-xf6glr2h.json key: cord-354620-xf6glr2h authors: Tian, Bin; Cai, Dongjie; He, Tianqiong; Deng, Liyao; Wu, Liping; Wang, Mingshu; Jia, Renyong; Zhu, Dekang; Liu, Mafeng; Yang, Qiao; Wu, Ying; Zhao, Xinxin; Chen, Shun; Zhang, Shaqiu; Huang, Juan; Ou, Xumin; Mao, Sai; Yu, Yanling; Zhang, Ling; Liu, Yunya; Cheng, Anchun title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date: 2020-01-28 journal: Front Immunol DOI: 10.3389/fimmu.2019.03131 sha: doc_id: 354620 cord_uid: xf6glr2h file: cache/cord-352150-ey9kc7zj.json key: cord-352150-ey9kc7zj authors: Degauque, Nicolas; Brouard, Sophie; Soulillou, Jean-Paul title: Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation date: 2016-03-24 journal: Front Immunol DOI: 10.3389/fimmu.2016.00089 sha: doc_id: 352150 cord_uid: ey9kc7zj file: cache/cord-352230-8mazd3eu.json key: cord-352230-8mazd3eu authors: Beeraka, Narasimha M.; Sadhu, Surya P.; Madhunapantula, SubbaRao V.; Rao Pragada, Rajeswara; Svistunov, Andrey A.; Nikolenko, Vladimir N.; Mikhaleva, Liudmila M.; Aliev, Gjumrakch title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 journal: Front Immunol DOI: 10.3389/fimmu.2020.552925 sha: doc_id: 352230 cord_uid: 8mazd3eu file: cache/cord-352737-3ttrx3lf.json key: cord-352737-3ttrx3lf authors: Cunha, Lucas Leite; Perazzio, Sandro Felix; Azzi, Jamil; Cravedi, Paolo; Riella, Leonardo Vidal title: Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response date: 2020-08-07 journal: Front Immunol DOI: 10.3389/fimmu.2020.01748 sha: doc_id: 352737 cord_uid: 3ttrx3lf file: cache/cord-354030-8tfg881h.json key: cord-354030-8tfg881h authors: Dong, Rong; Chu, Zhugang; Yu, Fuxun; Zha, Yan title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 journal: Front Immunol DOI: 10.3389/fimmu.2020.01784 sha: doc_id: 354030 cord_uid: 8tfg881h file: cache/cord-339152-wfakzb6w.json key: cord-339152-wfakzb6w authors: Trovato, Maria; Sartorius, Rossella; D’Apice, Luciana; Manco, Roberta; De Berardinis, Piergiuseppe title: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date: 2020-09-03 journal: Front Immunol DOI: 10.3389/fimmu.2020.02130 sha: doc_id: 339152 cord_uid: wfakzb6w file: cache/cord-343824-00mqmpzw.json key: cord-343824-00mqmpzw authors: Qian, Wei; Wei, Xiaoqin; Guo, Kelei; Li, Yongtao; Lin, Xian; Zou, Zhong; Zhou, Hongbo; Jin, Meilin title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 date: 2017-07-03 journal: Front Immunol DOI: 10.3389/fimmu.2017.00779 sha: doc_id: 343824 cord_uid: 00mqmpzw Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-frontImmunol-cord === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62598 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61718 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61673 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62183 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62537 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62525 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63121 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62540 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63340 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 61901 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62479 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62530 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63195 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64273 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64841 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63533 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64214 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63996 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64026 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64091 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64194 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64971 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64511 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 60781 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64092 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64518 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64142 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63370 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64354 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64215 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 62892 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 63890 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-004477-qu2o2iu1 author: Vlasova, Anastasia N. title: Editorial: Porcine Anti-Viral Immunity date: 2020-03-06 pages: extension: .txt txt: ./txt/cord-004477-qu2o2iu1.txt cache: ./cache/cord-004477-qu2o2iu1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004477-qu2o2iu1.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-267237-wbwlfx7q author: Gómez-Rial, Jose title: Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-267237-wbwlfx7q.txt cache: ./cache/cord-267237-wbwlfx7q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267237-wbwlfx7q.txt' === file2bib.sh === id: cord-262575-06i2nv0t author: Caracciolo, Massimo title: Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-262575-06i2nv0t.txt cache: ./cache/cord-262575-06i2nv0t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262575-06i2nv0t.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73204 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 72705 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-030803-6i0e2zkd author: Hu, Wan-Chung title: A Framework of All Discovered Immunological Pathways and Their Roles for Four Specific Types of Pathogens and Hypersensitivities date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-030803-6i0e2zkd.txt cache: ./cache/cord-030803-6i0e2zkd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-030803-6i0e2zkd.txt' === file2bib.sh === id: cord-280924-g6062fwk author: Hachim, Mahmood Yaseen title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-280924-g6062fwk.txt cache: ./cache/cord-280924-g6062fwk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280924-g6062fwk.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64708 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 73562 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-269170-9f460xbq author: Kaneko, Kazunari title: Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-269170-9f460xbq.txt cache: ./cache/cord-269170-9f460xbq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-269170-9f460xbq.txt' === file2bib.sh === id: cord-015254-xtox2rxs author: Li, Hao-Ling title: C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood–Spinal Cord Barrier date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-015254-xtox2rxs.txt cache: ./cache/cord-015254-xtox2rxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015254-xtox2rxs.txt' === file2bib.sh === id: cord-267567-w39f584z author: Pombo, Joao Palma title: Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections date: 2018-06-04 pages: extension: .txt txt: ./txt/cord-267567-w39f584z.txt cache: ./cache/cord-267567-w39f584z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267567-w39f584z.txt' === file2bib.sh === id: cord-295302-vwrxentv author: Shivarov, Velizar title: Potential SARS-CoV-2 Preimmune IgM Epitopes date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-295302-vwrxentv.txt cache: ./cache/cord-295302-vwrxentv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-295302-vwrxentv.txt' === file2bib.sh === id: cord-279105-e2zjxjox author: Lee, Cheryl Yi-Pin title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-279105-e2zjxjox.txt cache: ./cache/cord-279105-e2zjxjox.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279105-e2zjxjox.txt' /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-262375-1ex2ow07 author: Qun, Sen title: Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19 date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-262375-1ex2ow07.txt cache: ./cache/cord-262375-1ex2ow07.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262375-1ex2ow07.txt' === file2bib.sh === id: cord-003724-705h5l06 author: Di Lullo, Giulia title: Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris date: 2019-06-19 pages: extension: .txt txt: ./txt/cord-003724-705h5l06.txt cache: ./cache/cord-003724-705h5l06.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003724-705h5l06.txt' === file2bib.sh === id: cord-003545-corvd5cs author: Li, Chen title: Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus date: 2019-03-19 pages: extension: .txt txt: ./txt/cord-003545-corvd5cs.txt cache: ./cache/cord-003545-corvd5cs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003545-corvd5cs.txt' === file2bib.sh === id: cord-003685-jcvrqeew author: Gelain, Maria Elena title: Acute Phase Proteins in Marine Mammals: State of Art, Perspectives and Challenges date: 2019-05-29 pages: extension: .txt txt: ./txt/cord-003685-jcvrqeew.txt cache: ./cache/cord-003685-jcvrqeew.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003685-jcvrqeew.txt' === file2bib.sh === id: cord-257116-6td3efjw author: Zhou, Yanrong title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production date: 2017-08-09 pages: extension: .txt txt: ./txt/cord-257116-6td3efjw.txt cache: ./cache/cord-257116-6td3efjw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257116-6td3efjw.txt' === file2bib.sh === id: cord-265855-zf52vl11 author: Mayor-Ibarguren, Ander title: A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-265855-zf52vl11.txt cache: ./cache/cord-265855-zf52vl11.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-265855-zf52vl11.txt' === file2bib.sh === id: cord-003378-0ozhye9q author: Yu, Haijing title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression date: 2018-12-13 pages: extension: .txt txt: ./txt/cord-003378-0ozhye9q.txt cache: ./cache/cord-003378-0ozhye9q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003378-0ozhye9q.txt' === file2bib.sh === id: cord-268438-bjs5oliw author: Jin, Yilin title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination date: 2019-12-03 pages: extension: .txt txt: ./txt/cord-268438-bjs5oliw.txt cache: ./cache/cord-268438-bjs5oliw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268438-bjs5oliw.txt' === file2bib.sh === id: cord-260452-js4nr4d8 author: Yu, Junyang title: Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection date: 2017-10-31 pages: extension: .txt txt: ./txt/cord-260452-js4nr4d8.txt cache: ./cache/cord-260452-js4nr4d8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260452-js4nr4d8.txt' === file2bib.sh === id: cord-284867-p4jgyusp author: Schöler, Lara title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-284867-p4jgyusp.txt cache: ./cache/cord-284867-p4jgyusp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-284867-p4jgyusp.txt' === file2bib.sh === id: cord-254809-o454k6ae author: He, Bing title: The Metabolic Changes and Immune Profiles in Patients With COVID-19 date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-254809-o454k6ae.txt cache: ./cache/cord-254809-o454k6ae.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254809-o454k6ae.txt' === file2bib.sh === id: cord-283505-ousbar6c author: Horman, William S. J. title: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-283505-ousbar6c.txt cache: ./cache/cord-283505-ousbar6c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-283505-ousbar6c.txt' === file2bib.sh === id: cord-291941-9a4tt4f7 author: Barber-Axthelm, Isaac M. title: Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-291941-9a4tt4f7.txt cache: ./cache/cord-291941-9a4tt4f7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291941-9a4tt4f7.txt' === file2bib.sh === id: cord-261367-i1n8x0uc author: Hwang, Ji Young title: Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-261367-i1n8x0uc.txt cache: ./cache/cord-261367-i1n8x0uc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261367-i1n8x0uc.txt' === file2bib.sh === id: cord-000647-uofygmeu author: Stäger, Simona title: CD8(+) T Cells in Leishmania Infections: Friends or Foes? date: 2012-01-24 pages: extension: .txt txt: ./txt/cord-000647-uofygmeu.txt cache: ./cache/cord-000647-uofygmeu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000647-uofygmeu.txt' === file2bib.sh === id: cord-003656-7mzsaz7a author: Wium, Martha title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 pages: extension: .txt txt: ./txt/cord-003656-7mzsaz7a.txt cache: ./cache/cord-003656-7mzsaz7a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003656-7mzsaz7a.txt' === file2bib.sh === id: cord-268781-6l74rrlm author: Poh, Chek Meng title: Multiplex Screening Assay for Identifying Cytotoxic CD8(+) T Cell Epitopes date: 2020-03-11 pages: extension: .txt txt: ./txt/cord-268781-6l74rrlm.txt cache: ./cache/cord-268781-6l74rrlm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268781-6l74rrlm.txt' === file2bib.sh === id: cord-003368-f8f2utzx author: Lutterberg, Karina title: A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence date: 2018-12-06 pages: extension: .txt txt: ./txt/cord-003368-f8f2utzx.txt cache: ./cache/cord-003368-f8f2utzx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003368-f8f2utzx.txt' === file2bib.sh === id: cord-034310-izpt032p author: Chernomordik, Fernando title: The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-034310-izpt032p.txt cache: ./cache/cord-034310-izpt032p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 251 resourceName b'cord-034310-izpt032p.txt' === file2bib.sh === id: cord-003914-ss8vdpox author: Wang, Shenghua title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection date: 2019-10-02 pages: extension: .txt txt: ./txt/cord-003914-ss8vdpox.txt cache: ./cache/cord-003914-ss8vdpox.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-003914-ss8vdpox.txt' === file2bib.sh === id: cord-256582-x2grfhov author: Sung, Pei-Shan title: CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections date: 2019-12-06 pages: extension: .txt txt: ./txt/cord-256582-x2grfhov.txt cache: ./cache/cord-256582-x2grfhov.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-256582-x2grfhov.txt' === file2bib.sh === id: cord-001674-tp4o7fxx author: Oliveira, Cláudia C. title: Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome date: 2015-06-05 pages: extension: .txt txt: ./txt/cord-001674-tp4o7fxx.txt cache: ./cache/cord-001674-tp4o7fxx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001674-tp4o7fxx.txt' === file2bib.sh === id: cord-033488-du8heorx author: Ho, Thuong Thi title: Plant-Derived Trimeric CO-26K-Equivalent Epitope Induced Neutralizing Antibodies Against Porcine Epidemic Diarrhea Virus date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-033488-du8heorx.txt cache: ./cache/cord-033488-du8heorx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 26 resourceName b'cord-033488-du8heorx.txt' === file2bib.sh === id: cord-003825-tkqxb1ql author: Toman, Miroslav title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus date: 2019-08-06 pages: extension: .txt txt: ./txt/cord-003825-tkqxb1ql.txt cache: ./cache/cord-003825-tkqxb1ql.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003825-tkqxb1ql.txt' === file2bib.sh === id: cord-267134-5gz2dotn author: Sallenave, Jean-Michel title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-267134-5gz2dotn.txt cache: ./cache/cord-267134-5gz2dotn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267134-5gz2dotn.txt' === file2bib.sh === id: cord-259131-36udb7uc author: Hunegnaw, Ruth title: Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques date: 2019-07-03 pages: extension: .txt txt: ./txt/cord-259131-36udb7uc.txt cache: ./cache/cord-259131-36udb7uc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-259131-36udb7uc.txt' === file2bib.sh === id: cord-255578-0ltb9dpa author: Li, Xiangru title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-255578-0ltb9dpa.txt cache: ./cache/cord-255578-0ltb9dpa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255578-0ltb9dpa.txt' === file2bib.sh === id: cord-030385-btf502ju author: Sun, Zhiheng title: 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-030385-btf502ju.txt cache: ./cache/cord-030385-btf502ju.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-030385-btf502ju.txt' === file2bib.sh === id: cord-268511-dx2cqqt5 author: Kunkl, Martina title: CD28 Autonomous Signaling Orchestrates IL-22 Expression and IL-22-Regulated Epithelial Barrier Functions in Human T Lymphocytes date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-268511-dx2cqqt5.txt cache: ./cache/cord-268511-dx2cqqt5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268511-dx2cqqt5.txt' === file2bib.sh === id: cord-252568-b8sbvy0g author: Marques Neto, Lázaro Moreira title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date: 2017-03-08 pages: extension: .txt txt: ./txt/cord-252568-b8sbvy0g.txt cache: ./cache/cord-252568-b8sbvy0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-252568-b8sbvy0g.txt' === file2bib.sh === id: cord-284156-btb4oodz author: Liu, Yiliu title: Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity date: 2017-01-03 pages: extension: .txt txt: ./txt/cord-284156-btb4oodz.txt cache: ./cache/cord-284156-btb4oodz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284156-btb4oodz.txt' === file2bib.sh === id: cord-003319-u88gznxq author: Huang, Weishan title: Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages date: 2018-11-19 pages: extension: .txt txt: ./txt/cord-003319-u88gznxq.txt cache: ./cache/cord-003319-u88gznxq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003319-u88gznxq.txt' === file2bib.sh === id: cord-004151-9815ikzg author: Pan, Xiaocheng title: Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) date: 2020-01-08 pages: extension: .txt txt: ./txt/cord-004151-9815ikzg.txt cache: ./cache/cord-004151-9815ikzg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004151-9815ikzg.txt' === file2bib.sh === id: cord-257662-viy65y72 author: Burrack, Kristina S. title: The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases date: 2014-09-08 pages: extension: .txt txt: ./txt/cord-257662-viy65y72.txt cache: ./cache/cord-257662-viy65y72.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-257662-viy65y72.txt' === file2bib.sh === id: cord-268501-z4oztgi0 author: Palatnik-de-Sousa, Clarisa B. title: What Would Jenner and Pasteur Have Done About COVID-19 Coronavirus? The Urges of a Vaccinologist date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-268501-z4oztgi0.txt cache: ./cache/cord-268501-z4oztgi0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268501-z4oztgi0.txt' === file2bib.sh === id: cord-254192-86ksgl5t author: Li, Liang title: IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia date: 2019-10-17 pages: extension: .txt txt: ./txt/cord-254192-86ksgl5t.txt cache: ./cache/cord-254192-86ksgl5t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254192-86ksgl5t.txt' === file2bib.sh === id: cord-278839-uu2wlpmp author: Alberca, Ricardo Wesley title: Pregnancy, Viral Infection, and COVID-19 date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-278839-uu2wlpmp.txt cache: ./cache/cord-278839-uu2wlpmp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-278839-uu2wlpmp.txt' === file2bib.sh === id: cord-253108-p3wlw5d4 author: Olson, Brian M. title: Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance date: 2013-10-18 pages: extension: .txt txt: ./txt/cord-253108-p3wlw5d4.txt cache: ./cache/cord-253108-p3wlw5d4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 561 resourceName b'cord-253108-p3wlw5d4.txt' === file2bib.sh === id: cord-282336-zvc04s39 author: Choudhary, Ishita title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-282336-zvc04s39.txt cache: ./cache/cord-282336-zvc04s39.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282336-zvc04s39.txt' === file2bib.sh === id: cord-263141-n200x6z1 author: Zelaya, Hortensia title: Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection date: 2016-12-23 pages: extension: .txt txt: ./txt/cord-263141-n200x6z1.txt cache: ./cache/cord-263141-n200x6z1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263141-n200x6z1.txt' === file2bib.sh === id: cord-298458-p7rvupjo author: Schmidt, Megan E. title: The CD8 T Cell Response to Respiratory Virus Infections date: 2018-04-09 pages: extension: .txt txt: ./txt/cord-298458-p7rvupjo.txt cache: ./cache/cord-298458-p7rvupjo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298458-p7rvupjo.txt' === file2bib.sh === id: cord-032953-qy4b2l2f author: Picard-Sánchez, Amparo title: Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-032953-qy4b2l2f.txt cache: ./cache/cord-032953-qy4b2l2f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-032953-qy4b2l2f.txt' === file2bib.sh === id: cord-266085-914y3je0 author: Correa, Isabel title: Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells date: 2018-03-23 pages: extension: .txt txt: ./txt/cord-266085-914y3je0.txt cache: ./cache/cord-266085-914y3je0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-266085-914y3je0.txt' === file2bib.sh === id: cord-263433-oldy0gta author: Barriocanal, Marina title: Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin date: 2015-01-09 pages: extension: .txt txt: ./txt/cord-263433-oldy0gta.txt cache: ./cache/cord-263433-oldy0gta.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-263433-oldy0gta.txt' === file2bib.sh === id: cord-304619-tpv76833 author: Chatterjea, Devavani title: Teaching Immunology as a Liberal Art date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-304619-tpv76833.txt cache: ./cache/cord-304619-tpv76833.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304619-tpv76833.txt' === file2bib.sh === id: cord-316702-dj2fo8sn author: Vignesh, Ramachandran title: Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-316702-dj2fo8sn.txt cache: ./cache/cord-316702-dj2fo8sn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-316702-dj2fo8sn.txt' === file2bib.sh === id: cord-333670-qv1orlv5 author: Mutti, Luciano title: Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate? date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-333670-qv1orlv5.txt cache: ./cache/cord-333670-qv1orlv5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333670-qv1orlv5.txt' === file2bib.sh === id: cord-003122-a3f4l6iu author: Dou, Dan title: Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement date: 2018-07-20 pages: extension: .txt txt: ./txt/cord-003122-a3f4l6iu.txt cache: ./cache/cord-003122-a3f4l6iu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003122-a3f4l6iu.txt' === file2bib.sh === id: cord-298604-tn8hc6jv author: Khawaja, Akif A. title: Identification of a Novel HIF-1α-α(M)β(2) Integrin-NET Axis in Fibrotic Interstitial Lung Disease date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-298604-tn8hc6jv.txt cache: ./cache/cord-298604-tn8hc6jv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-298604-tn8hc6jv.txt' === file2bib.sh === id: cord-278081-tk7vn1v1 author: Brooks, Wesley H. title: Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date: 2017-11-28 pages: extension: .txt txt: ./txt/cord-278081-tk7vn1v1.txt cache: ./cache/cord-278081-tk7vn1v1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278081-tk7vn1v1.txt' === file2bib.sh === id: cord-313227-6zwkfzab author: Scala, Stefania title: Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-313227-6zwkfzab.txt cache: ./cache/cord-313227-6zwkfzab.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313227-6zwkfzab.txt' === file2bib.sh === id: cord-262944-9k64f0tw author: Parker, Elaine L. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-262944-9k64f0tw.txt cache: ./cache/cord-262944-9k64f0tw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262944-9k64f0tw.txt' === file2bib.sh === id: cord-305936-tdswzj7r author: Freitas, André Ricardo Ribas title: Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil date: 2018-01-08 pages: extension: .txt txt: ./txt/cord-305936-tdswzj7r.txt cache: ./cache/cord-305936-tdswzj7r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305936-tdswzj7r.txt' === file2bib.sh === id: cord-268483-joiajgs4 author: Shah, Vibhuti Kumar title: Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-268483-joiajgs4.txt cache: ./cache/cord-268483-joiajgs4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268483-joiajgs4.txt' === file2bib.sh === id: cord-318418-uqxzds6g author: Inatomi, Takio title: Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition date: 2017-12-22 pages: extension: .txt txt: ./txt/cord-318418-uqxzds6g.txt cache: ./cache/cord-318418-uqxzds6g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318418-uqxzds6g.txt' === file2bib.sh === id: cord-313117-0qur0isb author: Gardinassi, Luiz G. title: Immune and Metabolic Signatures of COVID-19 Revealed by Transcriptomics Data Reuse date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-313117-0qur0isb.txt cache: ./cache/cord-313117-0qur0isb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313117-0qur0isb.txt' === file2bib.sh === id: cord-304623-j9ay4jkf author: Entrican, Gary title: The Veterinary Immunological Toolbox: Past, Present, and Future date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-304623-j9ay4jkf.txt cache: ./cache/cord-304623-j9ay4jkf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-304623-j9ay4jkf.txt' === file2bib.sh === id: cord-003091-uvfppirt author: Gornati, Laura title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines date: 2018-06-27 pages: extension: .txt txt: ./txt/cord-003091-uvfppirt.txt cache: ./cache/cord-003091-uvfppirt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003091-uvfppirt.txt' === file2bib.sh === id: cord-328011-6lf3no6u author: Zayed, Hatem title: Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-328011-6lf3no6u.txt cache: ./cache/cord-328011-6lf3no6u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328011-6lf3no6u.txt' === file2bib.sh === id: cord-306600-cxz8hf9q author: Matarazzo, Laura title: Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia date: 2019-04-09 pages: extension: .txt txt: ./txt/cord-306600-cxz8hf9q.txt cache: ./cache/cord-306600-cxz8hf9q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306600-cxz8hf9q.txt' === file2bib.sh === id: cord-312074-0nqmjdek author: Zhong, Jixin title: Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease date: 2015-09-25 pages: extension: .txt txt: ./txt/cord-312074-0nqmjdek.txt cache: ./cache/cord-312074-0nqmjdek.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312074-0nqmjdek.txt' === file2bib.sh === id: cord-308433-vrkdtrfz author: Roberts, Ceri A. title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-308433-vrkdtrfz.txt cache: ./cache/cord-308433-vrkdtrfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308433-vrkdtrfz.txt' === file2bib.sh === id: cord-319774-mkz7z38o author: Hou, Dongni title: High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease date: 2016-08-31 pages: extension: .txt txt: ./txt/cord-319774-mkz7z38o.txt cache: ./cache/cord-319774-mkz7z38o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-319774-mkz7z38o.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-332150-j76726no author: De Stefano, Ludovico title: A “Window of Therapeutic Opportunity” for Anti-Cytokine Therapy in Patients With Coronavirus Disease 2019 date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-332150-j76726no.txt cache: ./cache/cord-332150-j76726no.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332150-j76726no.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-333932-aqcllik0 author: Diao, Bo title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-333932-aqcllik0.txt cache: ./cache/cord-333932-aqcllik0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333932-aqcllik0.txt' === file2bib.sh === id: cord-353217-gmc3qrci author: de Miranda Santos, Isabel Kinney Ferreira title: Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus date: 2020-08-04 pages: extension: .txt txt: ./txt/cord-353217-gmc3qrci.txt cache: ./cache/cord-353217-gmc3qrci.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353217-gmc3qrci.txt' === file2bib.sh === id: cord-340228-mvqoyror author: Al-Herz, Waleed title: Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry date: 2019-05-29 pages: extension: .txt txt: ./txt/cord-340228-mvqoyror.txt cache: ./cache/cord-340228-mvqoyror.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340228-mvqoyror.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 76714 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-323756-atnrw9ew author: Vabret, Nicolas title: Sensing Microbial RNA in the Cytosol date: 2013-12-25 pages: extension: .txt txt: ./txt/cord-323756-atnrw9ew.txt cache: ./cache/cord-323756-atnrw9ew.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323756-atnrw9ew.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 78936 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 79058 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 80372 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-351305-6vtv2xuh author: Schramm, Markus A. title: COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-351305-6vtv2xuh.txt cache: ./cache/cord-351305-6vtv2xuh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351305-6vtv2xuh.txt' === file2bib.sh === id: cord-328549-r56lih8j author: Okamoto, Masaaki title: Regulation of RIG-I Activation by K63-Linked Polyubiquitination date: 2018-01-05 pages: extension: .txt txt: ./txt/cord-328549-r56lih8j.txt cache: ./cache/cord-328549-r56lih8j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328549-r56lih8j.txt' === file2bib.sh === id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-328003-yovp8squ.txt cache: ./cache/cord-328003-yovp8squ.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328003-yovp8squ.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 79881 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-312955-gs65c3fy author: Schreiber, Gideon title: The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-312955-gs65c3fy.txt cache: ./cache/cord-312955-gs65c3fy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312955-gs65c3fy.txt' === file2bib.sh === id: cord-336924-7xcbtn3q author: Borghi, Maria Orietta title: Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-336924-7xcbtn3q.txt cache: ./cache/cord-336924-7xcbtn3q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336924-7xcbtn3q.txt' === file2bib.sh === id: cord-317797-h229skaq author: Li, Conglei title: Crosstalk Between Platelets and Microbial Pathogens date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-317797-h229skaq.txt cache: ./cache/cord-317797-h229skaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317797-h229skaq.txt' === file2bib.sh === id: cord-319729-6lzjhn8j author: Tian, Bin title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway date: 2018-01-19 pages: extension: .txt txt: ./txt/cord-319729-6lzjhn8j.txt cache: ./cache/cord-319729-6lzjhn8j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319729-6lzjhn8j.txt' === file2bib.sh === id: cord-350492-1s6wtj25 author: Ruscitti, Piero title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-350492-1s6wtj25.txt cache: ./cache/cord-350492-1s6wtj25.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350492-1s6wtj25.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 80691 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 81363 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-342776-hkjhqgie author: Jewett, Anahid title: The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-342776-hkjhqgie.txt cache: ./cache/cord-342776-hkjhqgie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-342776-hkjhqgie.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 79490 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-304626-ffao7vka author: Mellors, Jack title: Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-304626-ffao7vka.txt cache: ./cache/cord-304626-ffao7vka.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-304626-ffao7vka.txt' === file2bib.sh === id: cord-321401-w4ne60fn author: Schrumpf, Jasmijn A. title: Impact of the Local Inflammatory Environment on Mucosal Vitamin D Metabolism and Signaling in Chronic Inflammatory Lung Diseases date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-321401-w4ne60fn.txt cache: ./cache/cord-321401-w4ne60fn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-321401-w4ne60fn.txt' === file2bib.sh === id: cord-300429-b0zev8zb author: Sobocińska, Justyna title: Protein Palmitoylation and Its Role in Bacterial and Viral Infections date: 2018-01-19 pages: extension: .txt txt: ./txt/cord-300429-b0zev8zb.txt cache: ./cache/cord-300429-b0zev8zb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-300429-b0zev8zb.txt' === file2bib.sh === id: cord-352960-pfccsgco author: Gössling, Katharina L. title: Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome date: 2017-06-30 pages: extension: .txt txt: ./txt/cord-352960-pfccsgco.txt cache: ./cache/cord-352960-pfccsgco.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352960-pfccsgco.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 79029 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-354353-hyz0gmpz author: Farhangrazi, Z. Shadi title: Airborne Particulate Matter and SARS-CoV-2 Partnership: Virus Hitchhiking, Stabilization and Immune Cell Targeting — A Hypothesis date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-354353-hyz0gmpz.txt cache: ./cache/cord-354353-hyz0gmpz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-354353-hyz0gmpz.txt' === file2bib.sh === id: cord-338261-tyimwctm author: Farr, Laura title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-338261-tyimwctm.txt cache: ./cache/cord-338261-tyimwctm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338261-tyimwctm.txt' === file2bib.sh === id: cord-351431-xcqz9d3t author: Wang, Jun title: Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19 date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-351431-xcqz9d3t.txt cache: ./cache/cord-351431-xcqz9d3t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-351431-xcqz9d3t.txt' === file2bib.sh === id: cord-323590-m4jsu1q5 author: Ortiz de Landazuri, Iñaki title: Manufacturing and Management of CAR T-Cell Therapy in “COVID-19’s Time”: Central Versus Point of Care Proposals date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-323590-m4jsu1q5.txt cache: ./cache/cord-323590-m4jsu1q5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323590-m4jsu1q5.txt' === file2bib.sh === id: cord-325129-faptufak author: Meini, Simone title: Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key? date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-325129-faptufak.txt cache: ./cache/cord-325129-faptufak.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325129-faptufak.txt' === file2bib.sh === id: cord-350041-b1vmnwv2 author: Cena, Hellas title: Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection? date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-350041-b1vmnwv2.txt cache: ./cache/cord-350041-b1vmnwv2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350041-b1vmnwv2.txt' === file2bib.sh === id: cord-333041-69n2wwn3 author: Pal, Anandita title: Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-333041-69n2wwn3.txt cache: ./cache/cord-333041-69n2wwn3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333041-69n2wwn3.txt' === file2bib.sh === id: cord-320474-jyk7zphp author: Bonaventura, Aldo title: Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-320474-jyk7zphp.txt cache: ./cache/cord-320474-jyk7zphp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320474-jyk7zphp.txt' === file2bib.sh === id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-264814-v4wnmg03.txt cache: ./cache/cord-264814-v4wnmg03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264814-v4wnmg03.txt' === file2bib.sh === id: cord-341513-e6p3lrlf author: Li, Yunchuan title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection date: 2017-09-29 pages: extension: .txt txt: ./txt/cord-341513-e6p3lrlf.txt cache: ./cache/cord-341513-e6p3lrlf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-341513-e6p3lrlf.txt' === file2bib.sh === id: cord-330417-8nnobx8g author: Herrmann, Marissa title: Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-330417-8nnobx8g.txt cache: ./cache/cord-330417-8nnobx8g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-330417-8nnobx8g.txt' === file2bib.sh === id: cord-353594-z1vxamvp author: Gagiannis, Daniel title: Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-353594-z1vxamvp.txt cache: ./cache/cord-353594-z1vxamvp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353594-z1vxamvp.txt' === file2bib.sh === id: cord-344829-adlp2rjy author: de Rivero Vaccari, Juan Carlos title: The Inflammasome in Times of COVID-19 date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-344829-adlp2rjy.txt cache: ./cache/cord-344829-adlp2rjy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344829-adlp2rjy.txt' === file2bib.sh === id: cord-348283-7xorq5ce author: Naz, Anam title: Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-348283-7xorq5ce.txt cache: ./cache/cord-348283-7xorq5ce.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348283-7xorq5ce.txt' === file2bib.sh === id: cord-340475-h0q1m3ed author: Carnero, Elena title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs date: 2014-11-06 pages: extension: .txt txt: ./txt/cord-340475-h0q1m3ed.txt cache: ./cache/cord-340475-h0q1m3ed.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340475-h0q1m3ed.txt' === file2bib.sh === id: cord-318630-h6j7iqbm author: Sinha, Sushmita title: CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis date: 2015-12-10 pages: extension: .txt txt: ./txt/cord-318630-h6j7iqbm.txt cache: ./cache/cord-318630-h6j7iqbm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318630-h6j7iqbm.txt' === file2bib.sh === id: cord-344610-mqq6fmsp author: Waumans, Yannick title: The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis date: 2015-08-07 pages: extension: .txt txt: ./txt/cord-344610-mqq6fmsp.txt cache: ./cache/cord-344610-mqq6fmsp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344610-mqq6fmsp.txt' === file2bib.sh === id: cord-334564-bqh9jkds author: Raony, Ícaro title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-334564-bqh9jkds.txt cache: ./cache/cord-334564-bqh9jkds.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334564-bqh9jkds.txt' === file2bib.sh === id: cord-340741-bhxm4zua author: Nayak, Tapas Kumar title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 pages: extension: .txt txt: ./txt/cord-340741-bhxm4zua.txt cache: ./cache/cord-340741-bhxm4zua.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340741-bhxm4zua.txt' === file2bib.sh === id: cord-338092-barmkkwx author: Geginat, Jens title: Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets date: 2015-10-13 pages: extension: .txt txt: ./txt/cord-338092-barmkkwx.txt cache: ./cache/cord-338092-barmkkwx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-338092-barmkkwx.txt' === file2bib.sh === id: cord-338498-3238fz73 author: Kleen, Thomas-Oliver title: Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends” date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-338498-3238fz73.txt cache: ./cache/cord-338498-3238fz73.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338498-3238fz73.txt' === file2bib.sh === id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 pages: extension: .txt txt: ./txt/cord-307813-elom30nx.txt cache: ./cache/cord-307813-elom30nx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 10 resourceName b'cord-307813-elom30nx.txt' === file2bib.sh === id: cord-325353-tx6s4ggu author: Restori, Katherine H. title: Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma date: 2018-06-04 pages: extension: .txt txt: ./txt/cord-325353-tx6s4ggu.txt cache: ./cache/cord-325353-tx6s4ggu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325353-tx6s4ggu.txt' === file2bib.sh === id: cord-352737-3ttrx3lf author: Cunha, Lucas Leite title: Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-352737-3ttrx3lf.txt cache: ./cache/cord-352737-3ttrx3lf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352737-3ttrx3lf.txt' === file2bib.sh === id: cord-320431-0877trhh author: Frey, Andreas title: More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-320431-0877trhh.txt cache: ./cache/cord-320431-0877trhh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320431-0877trhh.txt' === file2bib.sh === id: cord-354030-8tfg881h author: Dong, Rong title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-354030-8tfg881h.txt cache: ./cache/cord-354030-8tfg881h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354030-8tfg881h.txt' === file2bib.sh === id: cord-313431-swkcdvx8 author: Becerra-Diaz, Mireya title: Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-313431-swkcdvx8.txt cache: ./cache/cord-313431-swkcdvx8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313431-swkcdvx8.txt' === file2bib.sh === id: cord-344093-3bniy5b5 author: Peteranderl, Christin title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 pages: extension: .txt txt: ./txt/cord-344093-3bniy5b5.txt cache: ./cache/cord-344093-3bniy5b5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-344093-3bniy5b5.txt' === file2bib.sh === id: cord-339152-wfakzb6w author: Trovato, Maria title: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-339152-wfakzb6w.txt cache: ./cache/cord-339152-wfakzb6w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339152-wfakzb6w.txt' === file2bib.sh === id: cord-336201-fl606l3b author: Daryabor, Gholamreza title: The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-336201-fl606l3b.txt cache: ./cache/cord-336201-fl606l3b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336201-fl606l3b.txt' === file2bib.sh === id: cord-256998-or73in8m author: Nguyen, Khue G. title: Localized Interleukin-12 for Cancer Immunotherapy date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-256998-or73in8m.txt cache: ./cache/cord-256998-or73in8m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-256998-or73in8m.txt' Que is empty; done journal-frontImmunol-cord === reduce.pl bib === id = cord-268781-6l74rrlm author = Poh, Chek Meng title = Multiplex Screening Assay for Identifying Cytotoxic CD8(+) T Cell Epitopes date = 2020-03-11 pages = extension = .txt mime = text/plain words = 6116 sentences = 312 flesch = 50 summary = Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8 + T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8 + T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Splenocytes from vaccinated mice challenged by a lethal PR8 infection were used to measure epitope-specific CD8 T cell effector functions through direct (in vivo cytotoxicity) and indirect (IFNγ-ICS) assays. cache = ./cache/cord-268781-6l74rrlm.txt txt = ./txt/cord-268781-6l74rrlm.txt === reduce.pl bib === id = cord-001674-tp4o7fxx author = Oliveira, Cláudia C. title = Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome date = 2015-06-05 pages = extension = .txt mime = text/plain words = 6630 sentences = 347 flesch = 46 summary = An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. This intramembrane proteolysis by SPP is thought to be important for the clearance of the ER membrane by removing small protein remnants anchored at FIGURE 1 | Classical and alternative pathways for MHC class I presentation. Furin-processed antigens targeted to the secretory route were presented by MHC class I at the cell surface and could elicit functional CD8 T-cell responses in vivo in a TAP-independent fashion (75, 81) . Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins cache = ./cache/cord-001674-tp4o7fxx.txt txt = ./txt/cord-001674-tp4o7fxx.txt === reduce.pl bib === id = cord-003656-7mzsaz7a author = Wium, Martha title = DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date = 2019-05-14 pages = extension = .txt mime = text/plain words = 5575 sentences = 308 flesch = 53 summary = Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. In this study we report, for the first time, that a DNA vaccine can elicit a humoral immune response in ostriches using OppA as antigen. The controls were serum samples representing the week 0, 3, 6, and 9 sampling points of a single ostrich, randomly selected from the pCI-neo_oppA 1,200 µg group based on high titers produced after vaccination. In this study, DNA vaccines were developed for ostriches using the oppA gene of an ostrich-infecting mycoplasma (Ms03) as vaccine antigen. cache = ./cache/cord-003656-7mzsaz7a.txt txt = ./txt/cord-003656-7mzsaz7a.txt === reduce.pl bib === id = cord-003091-uvfppirt author = Gornati, Laura title = Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines date = 2018-06-27 pages = extension = .txt mime = text/plain words = 9424 sentences = 460 flesch = 40 summary = Taking advantage of new adjuvants, innovative ags-delivery carriers and targeting strategies, it is now feasible to optimize the activation and ag presentation processes by the specific DCs subset that is the most effective in the initiation of the adaptive response needed in a given context. Indeed, MF59, an oil-in-water emulsion adjuvant, that allows long-lasting ag retention in draining LN and enhanced ag uptake by LN-resident DCs, promotes robust humoral responses via follicular DC activation (43) and CD4 + T cell immunity induction (44) . In addition to the use of NPs, targeting DC-specific receptors has become an attractive strategy for vaccine development due to the enforced efficiency of immune responses when compared to generic-delivering approaches. Moreover, vaccines based on the filamentous bacteriophage fd presenting an αDEC-205 scFv, efficiently induce DCs maturation via the activation of the TLR9-MyD88 pathway (144) , without adjuvants and further elicit potent antitumor responses when compared to non-tailored ag delivery (145) . cache = ./cache/cord-003091-uvfppirt.txt txt = ./txt/cord-003091-uvfppirt.txt === reduce.pl bib === id = cord-030803-6i0e2zkd author = Hu, Wan-Chung title = A Framework of All Discovered Immunological Pathways and Their Roles for Four Specific Types of Pathogens and Hypersensitivities date = 2020-08-07 pages = extension = .txt mime = text/plain words = 3125 sentences = 216 flesch = 49 summary = STAT5a and STAT5b have distinct target genes in immune responses (15) , and STAT5b is the transcription factor that induces Tfh. Tfh can induce B-cells to produce IgM antibodies and IL-21 produced by Tfh facilitates B cell isotype switching to IgG (16, 17) . Type 2 myeloid dendritic cells (CD141+ mDC2) are the antigen presenting cells Eradicable immune responses include TH1, TH2, TH17, and THαβ. Initiation of eradicable immunity also requires innate lymphoid cells to produce the initial cytokines that drive different immunological pathways. THαβ immune responses against self-antigens present as type 2 antibody-dependent cytotoxic hypersensitivity, such as the acute stage of myasthenia gravis or Graves' disease (37) . The effector cells of TH1-like immune responses include suppressive macrophages (M2), ILC1, suppressive CD8 T cells (CD28-CD8+Treg), IgA1producing B-cells, iNKT1 cells, and IFN-γ-/TGF-β-producing CD4 T cells (24, 40, 56) . TH3 immune responses induce type 2 antibody-dependent cytotoxic hypersensitivity, including the chronic stage of Systemic Lupus Erythematosus (SLE) (69) . cache = ./cache/cord-030803-6i0e2zkd.txt txt = ./txt/cord-030803-6i0e2zkd.txt === reduce.pl bib === id = cord-003319-u88gznxq author = Huang, Weishan title = Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages date = 2018-11-19 pages = extension = .txt mime = text/plain words = 6298 sentences = 313 flesch = 53 summary = To determine whether co-expression of LAG3 and CD49b is exclusive to Foxp3 − Tr1 cell subset, we infected IL-10 GFP /Foxp3 RFP dual reporter mice with Nb, and analyzed the IL-10-producing T cells. Along with the model of parasitic infection shown in Figure 2 , our data suggest that co-expression of LAG3 and CD49b marks all IL-10-producing T cell lineages in the pulmonary system, and relative abundance of the marked T cell subsets is dependent on the type of immune response as shown in the disease models. Despite the shared feature of co-expression of LAG3 and CD49b by IL-10-producing Foxp3 + CD4 + , Foxp3 − CD4 + , and CD8 + T cells, we also observed interesting discrepancies in the proportional composition of these three IL-10 high T cell subsets that are all LAG3/CD49b double positive in the lung mucosa of different pulmonary inflammatory disease models, as well as in different anatomical locations in the same mice upon TCR activation in vivo. cache = ./cache/cord-003319-u88gznxq.txt txt = ./txt/cord-003319-u88gznxq.txt === reduce.pl bib === id = cord-003378-0ozhye9q author = Yu, Haijing title = Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression date = 2018-12-13 pages = extension = .txt mime = text/plain words = 5912 sentences = 350 flesch = 53 summary = In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells (PBMCs) and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease (13, 14) . Compared to wild-type mice, CC10-knockout mice exhibited excessive airway inflammation Abbreviations: FH, fulminant hepatitis; MHV-3, murine hepatitis virus strain 3; Fgl2, Fibrinogen-like protein 2; CC10, Clara cell 10 KDa protein; ALF, acute liver failure; PFU, plaque-forming units; PBS, phosphate-buffered saline; ALT, alanine aminotransferase; AST, aspartate aminotransferase; PCA, pro-coagulant activity; HRP, horseradish peroxidase; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. In this study, we investigated the role of CC10 in hepatitis virus strain 3 (MHV-3)-induced FH in mice and explored whether CC10 protein could regulate Fgl2 in the disease process. cache = ./cache/cord-003378-0ozhye9q.txt txt = ./txt/cord-003378-0ozhye9q.txt === reduce.pl bib === id = cord-004151-9815ikzg author = Pan, Xiaocheng title = Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) date = 2020-01-08 pages = extension = .txt mime = text/plain words = 6365 sentences = 371 flesch = 56 summary = To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. In an attempt to identify anti-PRRSV CTL epitopes in this study, first, predicted peptide epitopes derived from PRRSV were synthesized, and a trimolecular complex, the structure of the epitope from PRRSV-NSP9 (TMPPGFELY, termed NSP9-TMP9)-bound SLA-1 * 1502 (pSLA-1 * 1502), was solved. The purified complex (44 kDa) of pSLA-1 * 1502 with the NSP9-TMP9 peptide (amino acid sequence TMPPGFELY, derived from residues 198-206 of the PRRSV non-structural protein) was dialyzed against crystallization buffer (20 mM Tris-HCl pH 8.0, 50 mM NaCl) and concentrated to 12 mg/mL. cache = ./cache/cord-004151-9815ikzg.txt txt = ./txt/cord-004151-9815ikzg.txt === reduce.pl bib === id = cord-003368-f8f2utzx author = Lutterberg, Karina title = A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence date = 2018-12-06 pages = extension = .txt mime = text/plain words = 5053 sentences = 287 flesch = 46 summary = After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. As other authors claimed the possibility of a genetic predisposition of BNP dams for production of BNP inducing alloantibodies (22) (23) (24) , our studies focused on investigating a general difference in immune responses between PregSure BVD vaccinated control cows and BNP donors. In in vitro proliferation assays with T cell mitogen ConA we observed that 22% of the unvaccinated cows reacted similar to BNP dams by showing a hyperproliferative reaction to ConA (immune deviant (ID) phenotype; Figure 6A , reaction difference ID to controls or BNP to controls, * * * * p < 0.0001). cache = ./cache/cord-003368-f8f2utzx.txt txt = ./txt/cord-003368-f8f2utzx.txt === reduce.pl bib === === reduce.pl bib === id = cord-003545-corvd5cs author = Li, Chen title = Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus date = 2019-03-19 pages = extension = .txt mime = text/plain words = 4512 sentences = 258 flesch = 45 summary = The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV). Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs. In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition. Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle. To analyze the gene expression profiles in response to different viral infections, the transcription levels of EcAtg5 were examined in RGNNV or SGIV infected cells. The results showed that EcAtg5 plays crucial roles in virus replication via promoting autophagy, down-regulating antiviral IFN responses, and affecting cell cycle. cache = ./cache/cord-003545-corvd5cs.txt txt = ./txt/cord-003545-corvd5cs.txt === reduce.pl bib === id = cord-033488-du8heorx author = Ho, Thuong Thi title = Plant-Derived Trimeric CO-26K-Equivalent Epitope Induced Neutralizing Antibodies Against Porcine Epidemic Diarrhea Virus date = 2020-09-16 pages = extension = .txt mime = text/plain words = 5435 sentences = 267 flesch = 47 summary = (A) Sera from five mice from each group immunized with a negative control (wild-type crude extract, G1) or a positive control (commercial vaccine, G2) or the crude extract containing COE-GCN4pII (G3) were mixed, diluted 200 times and used as a primary antibody for detecting 1 µg of purified PEDV antigen. Different levels of PEDV-specific IgG (B), IgA (C), and IgM (D) antibodies in each mouse sera group were calculated as the reciprocal of the geometric mean titer of the five mice of each group vaccinated with the negative control (wild-type crude extract, G1) or the positive control (commercial vaccine, G2) or the crude extract containing COE-GCN4pII (G3). Therefore, plant crude extract containing the trimeric COE protein had the level of IgG antibodies similar to that of commercial vaccines against the PEDV DR13 strain after the third injection. Therefore, we concluded that plant crude extract containing the trimeric COE protein had a strong immunogenicity and induced a neutralizing antibody titer similar to that of the commercial vaccine against the attenuated PEDV DR13 strain. cache = ./cache/cord-033488-du8heorx.txt txt = ./txt/cord-033488-du8heorx.txt === reduce.pl bib === id = cord-253108-p3wlw5d4 author = Olson, Brian M. title = Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance date = 2013-10-18 pages = extension = .txt mime = text/plain words = 7447 sentences = 260 flesch = 36 summary = Following more than a decade of studies aimed at elucidating the mechanisms that mediate Treg activity, interest was rekindled in the mid-1990s with the transformational research of Sakaguchi and colleagues, who specifically identified a population of CD4+CD25+ T cells that had suppressive function, which were coined as naturally occurring thymic-derived Tregs, or natural Abbreviations: APC, antigen-presenting cell; DC, dendritic cell; EAE, experimental autoimmune encephalitis; Ebi3, Epstein-Barr virus-induced gene 3; IL, interleukin; iTreg, induced regulatory T cell; NIMA, non-inherited maternal antigen; NK, natural killer; nTreg, natural regulatory T cell; PAP, prostatic acid phosphatase; TGF, transforming growth factor; Treg, regulatory T cell. When activated in these conditions, iTregs gain potent suppressive functions, inhibiting T-cell proliferation and effector functions in an antigen non-specific fashion, and play a central role in mediating regulation and propagating infectious tolerance in a variety of malignancies, including infectious diseases and cancer. cache = ./cache/cord-253108-p3wlw5d4.txt txt = ./txt/cord-253108-p3wlw5d4.txt === reduce.pl bib === id = cord-267134-5gz2dotn author = Sallenave, Jean-Michel title = Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date = 2020-05-28 pages = extension = .txt mime = text/plain words = 5347 sentences = 239 flesch = 39 summary = The first anatomical/histological reports from the lungs of severely SARS-CoV-2-affected patients experiencing acute respiratory disease syndrome (ARDS) revealed excessive inflammatory activation and destruction of the bronchial and alveolar epithelium, features already observed during the first SARS pandemics in 2003 (3, 4). The following sections will give an overview of the molecular and cellular mechanisms underpinning SARS-CoV virus infections and how lung and systemic host innate immune responses affect survival either positively, through downregulating the initial viral load, or negatively, by triggering uncontrolled inflammation. Regarding the lung, the differentiated Calu-3 cell line [when cultured at the air-liquid interface (ALI)] is the model of choice: in that set-up, SARS-CoV infection triggered an inflammatory response characterized by increased production of interleukin (IL)-6, IL-8, gamma interferon (IFN-γ), inducible protein 10 (IP-10), and activation of the transcription factor NF-κB (56) . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus cache = ./cache/cord-267134-5gz2dotn.txt txt = ./txt/cord-267134-5gz2dotn.txt === reduce.pl bib === id = cord-268501-z4oztgi0 author = Palatnik-de-Sousa, Clarisa B. title = What Would Jenner and Pasteur Have Done About COVID-19 Coronavirus? The Urges of a Vaccinologist date = 2020-08-26 pages = extension = .txt mime = text/plain words = 6331 sentences = 280 flesch = 46 summary = In fact, by May 11th, 2020 seven vaccines had already entered Phase I clinical trials: (1) encapsulated mRNA encoding protein S (Moderna and NIAID, USA); (2) Adenovirus expressing protein S (Cansino Biologics, China); (3) DCs modified with lentivirus expressing several proteins and CTLs (Shenzen Geno-Immune Medical, China); (4) an APC modified with lentivirus expressing several viral proteins (35); (5) Inno 4800, SARS CoV2 DNA Injection (Innovio, USA); (6) ChAdOx1 vaccine from the Jenner Institute, Oxford University, (UK) which is a genetically modified Adenovirus expressing Coronavirus proteins (39) , and is also being tested in a Phase II trial; and finally (7) the whole inactivated coronavirus with Alum by Sinovac, China (40) . Furthermore, in vaccinated monkeys, seven days after infection, the Sinovac inactivated vaccine at 6 µg/dose induced high titers of IgG antibodies directed against the S, RBD and lower levels of anti-N protein antibodies, high titers of virus neutralizing antibodies with no detected antibodydependent enhancement of disease (ADE) (40) . cache = ./cache/cord-268501-z4oztgi0.txt txt = ./txt/cord-268501-z4oztgi0.txt === reduce.pl bib === id = cord-003825-tkqxb1ql author = Toman, Miroslav title = Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus date = 2019-08-06 pages = extension = .txt mime = text/plain words = 6723 sentences = 395 flesch = 49 summary = The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Comparison of serum and oral fluid antibody responses after vaccination with modified live (MLV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in PRRS endemic farms cache = ./cache/cord-003825-tkqxb1ql.txt txt = ./txt/cord-003825-tkqxb1ql.txt === reduce.pl bib === id = cord-000647-uofygmeu author = Stäger, Simona title = CD8(+) T Cells in Leishmania Infections: Friends or Foes? date = 2012-01-24 pages = extension = .txt mime = text/plain words = 6676 sentences = 307 flesch = 46 summary = However, since CTLs have been www.frontiersin.org observed in various mouse models and also in human patients, a possible protective role for Leishmania-specific cytotoxic T cells should not be excluded. major infection became less important also because of the strong evidence that Th1 cells were the primary cells involved in mediating protection against cutaneous leishmaniasis (Reiner and Locksley, 1995; Louis et al., 1998; Sacks and Noben-Trauth, 2002) . Vaccination of humans with heat-killed Leishmania or recombinant parasite proteins has so far failed to induce long-term immunity and only recovery from natural or experimental infection has provided proper protection. Pilot studies in the murine model of VL have also demonstrated that adoptive transfer of antigen-specific CD8 + T cells (Polley et al., 2006) or reactivation of CD8 + T cell responses through a therapeutic vaccine (Joshi et al., 2009) results in the control of parasite growth. cache = ./cache/cord-000647-uofygmeu.txt txt = ./txt/cord-000647-uofygmeu.txt === reduce.pl bib === id = cord-015254-xtox2rxs author = Li, Hao-Ling title = C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood–Spinal Cord Barrier date = 2020-03-20 pages = extension = .txt mime = text/plain words = 4506 sentences = 221 flesch = 44 summary = We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. In this study, we examined the integrity of the BSCB and the migration of circulating immune cells into the spinal cord after chronic constriction injury (CCI) of the sciatic nerve, which induces neuropathic pain. To the best of our knowledge, it is the first study to report that blocking CXCL10/CXCR3 signaling attenuates the increases in BSCB permeability and T cell infiltration of the spinal cord induced by peripheral nerve injury. Previous studies have indicated that increased BSCB permeability is a prerequisite for immune cell infiltration of the spinal cord during the development of neuropathic pain (41) , and we found that blocking CXCL10/CXCR3 signaling with anti-CXCL10 antibodies reduced the BSCB's permeability to NaFlu, which suggests that CXCL10/CXCR3 signaling plays a critical role in CCI-induced BSCB dysfunction. cache = ./cache/cord-015254-xtox2rxs.txt txt = ./txt/cord-015254-xtox2rxs.txt === reduce.pl bib === id = cord-257662-viy65y72 author = Burrack, Kristina S. title = The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases date = 2014-09-08 pages = extension = .txt mime = text/plain words = 9002 sentences = 391 flesch = 33 summary = Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). In this review, we highlight recent studies of viral infections where myeloid cell polarization -resulting in expression of iNOS or Arg1 -contribute to viral control or the development of chronic virus infection and mediate the resolution of tissue damage or cause immunopathology. It was further shown that genetic deletion of myeloid cell Arg1 resulted in enhanced viral control in inflamed muscle tissue and reduced tissue pathology following RRV infection in mice (69) , suggesting an important role for Arg1-expressing macrophages in the persistence of these chronic viruses. In the absence of iNKT cells, influenza A (PR/8 strain) infection was shown to induce the expansion of CD11b + GR-1 + MDSCs in the lungs of mice, which suppressed influenza-specific T cell and antibody responses through the activity of both arginase and NOS, resulting in higher viral titers and increased mortality (81) . cache = ./cache/cord-257662-viy65y72.txt txt = ./txt/cord-257662-viy65y72.txt === reduce.pl bib === id = cord-267567-w39f584z author = Pombo, Joao Palma title = Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections date = 2018-06-04 pages = extension = .txt mime = text/plain words = 4034 sentences = 217 flesch = 32 summary = Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests counter strategies employed by host cells, which actively modulate several of these networks in response to infection, enhancing interferon signaling by doing so, and thus creating an antiviral environment. In this review, we discuss recent data on mechanisms of alteration of lipid metabolic pathways during infection by flaviviruses, with a focus on cholesterol and fatty acid biosynthesis, which can be manipulated by the invading viruses to support replication, but can also be modulated by the host immune system itself, as a means to fight infection. cache = ./cache/cord-267567-w39f584z.txt txt = ./txt/cord-267567-w39f584z.txt === reduce.pl bib === id = cord-003122-a3f4l6iu author = Dou, Dan title = Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement date = 2018-07-20 pages = extension = .txt mime = text/plain words = 10272 sentences = 565 flesch = 43 summary = The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. Influenza A viruses (IAVs) and type B viruses (IBVs) contain 8, negative-sense, single-stranded viral RNA (vRNA) gene segments ( Figure 1A ) (3, 4) , which encode transcripts for 10 essential viral proteins, as well as several strain-dependent accessory proteins ( Figure 1B) . In contrast to the early steps in IAV entry, vRNP trafficking to the nucleus following the fusion event is highly dependent on the host cell machinery and transport pathways [reviewed in Ref. cache = ./cache/cord-003122-a3f4l6iu.txt txt = ./txt/cord-003122-a3f4l6iu.txt === reduce.pl bib === id = cord-255578-0ltb9dpa author = Li, Xiangru title = Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date = 2020-06-19 pages = extension = .txt mime = text/plain words = 6400 sentences = 404 flesch = 55 summary = title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. In this study, Cfhr1 was deleted on C57BL/6 mouse to study the function of FHR-E on AP and the effect of FHR-E deficiency on LPS-induced sepsis. cache = ./cache/cord-255578-0ltb9dpa.txt txt = ./txt/cord-255578-0ltb9dpa.txt === reduce.pl bib === id = cord-262575-06i2nv0t author = Caracciolo, Massimo title = Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome date = 2020-08-25 pages = extension = .txt mime = text/plain words = 2163 sentences = 139 flesch = 40 summary = title: Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome Severe cases of COVID-19 present with serious lung inflammation, acute respiratory distress syndrome and multiorgan damage. SARS-CoV-2 infection is associated with high cytokine levels, including interleukin-6 and certain subsets of immune cells, in particular, NK, distinguished according to the cell surface density of CD56. Cytokine levels are inversely correlated with lymphocyte count, therefore cytokine release syndrome may be an impediment to the adaptive immune response against SARS-CoV-2 infection. An 85 year old male presenting in our hospital with COVID-19, whose condition was complicated by acute respiratory distress syndrome and cardiac and renal failure (with oliguria) after 25 days of hospitalization, was intubated and received canakinumab for compassionate use. The immune response, including the release of pro-inflammatory cytokines and activation of T cells, are essential for controlling the viral spread, inflammation, and tissue renewal (5, 6) . cache = ./cache/cord-262575-06i2nv0t.txt txt = ./txt/cord-262575-06i2nv0t.txt === reduce.pl bib === id = cord-261367-i1n8x0uc author = Hwang, Ji Young title = Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date = 2020-09-25 pages = extension = .txt mime = text/plain words = 7609 sentences = 309 flesch = 47 summary = Instead, mice with iBALT had reduced Th2-associated mRNA expression, less eosinophil recruitment to the lungs and airways, attenuated goblet cell hyperplasia and reduced mucus production following pulmonary sensitization and challenge with OVA. To test the effect of iBALT on the immune response to a pulmonary allergen, we administered LPS (or PBS) to neonatal mice as described above, allowed the mice to rest until they were 7 weeks old, then intranasally sensitized the iBALT and control groups with 100 µg OVA in combination with low dose (0.1 µg) LPS on days 49, 50, and 51 and challenged them on days 63, 64, 67, and 68 with 25 µg OVA ( Figure 1E ). Together, these data suggest that the spatial distribution of effector Th2 cells and Tregs is affected by the presence of iBALT (they cluster together), which may explain how iBALT and control mice can have similar numbers of Th2 cells in their lungs, but have so profoundly different outcomes in terms of eosinophil accumulation and histopathology. cache = ./cache/cord-261367-i1n8x0uc.txt txt = ./txt/cord-261367-i1n8x0uc.txt === reduce.pl bib === id = cord-259131-36udb7uc author = Hunegnaw, Ruth title = Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques date = 2019-07-03 pages = extension = .txt mime = text/plain words = 7426 sentences = 376 flesch = 46 summary = AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. In addition, the low proinflammatory cytokine response in chronic infection was not associated with an increase in IL-10-expressing AMs. To investigate AM activation, BAL cells obtained from naïve and acute and chronically infected macaques at weeks 2, 4, 8, 12, and 20 wpi, were incubated with native gp120 from R5 tropic SIV or LPS for 6 h, and intracellular expression of MIP-1β and IL-6 was assessed (Figures 3A,B) . Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals cache = ./cache/cord-259131-36udb7uc.txt txt = ./txt/cord-259131-36udb7uc.txt === reduce.pl bib === id = cord-284156-btb4oodz author = Liu, Yiliu title = Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity date = 2017-01-03 pages = extension = .txt mime = text/plain words = 7021 sentences = 397 flesch = 38 summary = Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. They function as cytoplasmic sensors for the recognition of a variety of RNA viruses and subsequent activation of downstream signaling to drive type I IFN production and antiviral gene expressions. (c) Interactions between RIG-I-TRIM25 complex and 14-3-3ϵ promote RIG-I translocation to mitochondrial mitochondrial antiviral signaling protein (MAVS) for downstream signaling, leading to interferon production. Protein purification and mass spectrometry analysis identified that phosphorylation of Thr170 in the CARDs antagonizes RIG-I signaling by inhibiting TRIM25-mediated Lys172 ubiquitination and MAVS binding (68) . Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling Inhibition of dengue and chikungunya virus infections by RIG-I-mediated type I interferon-independent stimulation of the innate antiviral response cache = ./cache/cord-284156-btb4oodz.txt txt = ./txt/cord-284156-btb4oodz.txt === reduce.pl bib === id = cord-030385-btf502ju author = Sun, Zhiheng title = 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date = 2020-07-22 pages = extension = .txt mime = text/plain words = 5855 sentences = 328 flesch = 55 summary = However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively. cache = ./cache/cord-030385-btf502ju.txt txt = ./txt/cord-030385-btf502ju.txt === reduce.pl bib === id = cord-262375-1ex2ow07 author = Qun, Sen title = Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19 date = 2020-09-02 pages = extension = .txt mime = text/plain words = 5187 sentences = 280 flesch = 50 summary = All confirmed patients were clinically classified according to the "Novel Coronavirus Pneumonia Treatment Scheme of the National Health Commission of the People's Republic of China (version 7)" at the time of admission (4), as follows: (1) general type: symptoms such as fever and respiratory tract complaints were present, and manifestations of pneumonia could be seen on imaging; (2) serious type: any of the following criteria were met: (1) respiratory distress, respiratory rate (RR) ≥ 30 times/min; (2) resting oxygen saturation ≤ 93%; or (3) arterial partial oxygen pressure (PaO 2 )/oxygen absorption concentration (FiO 2 ) ≤ 300 mmHg (1 mmHg = 0.133 kPa); (3) critical type: any of the following criteria were met: (1) respiratory failure and a need for mechanical ventilation, (2) shock, or (3) a combination of factors with other organ failure requiring ICU care. cache = ./cache/cord-262375-1ex2ow07.txt txt = ./txt/cord-262375-1ex2ow07.txt === reduce.pl bib === id = cord-257116-6td3efjw author = Zhou, Yanrong title = Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production date = 2017-08-09 pages = extension = .txt mime = text/plain words = 5514 sentences = 323 flesch = 50 summary = title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEVencoded proteins. Nsp14 interacts with cellular DExD/H helicase DDX1 to activate IFN-β in a NF-κB dependent manner, and DDX1 is associated with TGEV-induced IFN-β production, revealing a potential coactivator role of host RNA helicase DDX1 on virus and viral protein induced innate immune responses. cache = ./cache/cord-257116-6td3efjw.txt txt = ./txt/cord-257116-6td3efjw.txt === reduce.pl bib === id = cord-298458-p7rvupjo author = Schmidt, Megan E. title = The CD8 T Cell Response to Respiratory Virus Infections date = 2018-04-09 pages = extension = .txt mime = text/plain words = 8953 sentences = 402 flesch = 37 summary = CD8 T cells play a critical role in mediating viral clearance following many respiratory virus infections including RSV, IAV, and HMPV (25) (26) (27) . In addition, recent murine studies utilizing CD8 T cell epitope-specific immunization strategies observed significantly reduced lung viral titers following IAV, RSV, or SARS challenges (28) (29) (30) . Prime-boosted mice exhibited significantly reduced lung viral titers following RSV, IAV, or SARS infections compared to controls lacking virus-specific memory CD8 T cells. In addition to causing disease in acute respiratory infections, IFN-γ produced by memory CD8 T cells mediated the severe and fatal immunopathology following RSV infection of DC-LM prime-boosted mice (30) . Additionally, robust memory CD8 T cell responses efficiently reduced lung viral titers in the absence of neutralizing antibodies following RSV, IAV, or SARS secondary infections. Despite their benefits in mediating viral clearance and providing protection against secondary infections, memory CD8 T cell responses have been associated with the induction of immunopathology following respiratory virus infections. cache = ./cache/cord-298458-p7rvupjo.txt txt = ./txt/cord-298458-p7rvupjo.txt === reduce.pl bib === id = cord-004477-qu2o2iu1 author = Vlasova, Anastasia N. title = Editorial: Porcine Anti-Viral Immunity date = 2020-03-06 pages = extension = .txt mime = text/plain words = 1583 sentences = 88 flesch = 45 summary = Immediately following viral infection, neonatal survival depends on innate immunity and passive protection by lactogenic immune factors such as pathogen-specific antibodies, until an adaptive immune response can develop. Wide-spread porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV) represent major health challenges in the large US swine production systems and possibly worldwide. In introducing the topic of anti-viral immunity, we emphasize the genetic diversity of viruses, the virus life cycle and the pathology that viral infection can cause. A more tedious procedure is to use only parts of the virus as the vaccine (subunit vaccines) that target the immune response to those viral epitopes that elicit VN antibodies. A second approach to vaccine development is use of live attenuated virus that has been genetically modified or cell culture adapted and cannot produce a disease in the host but can still replicate. cache = ./cache/cord-004477-qu2o2iu1.txt txt = ./txt/cord-004477-qu2o2iu1.txt === reduce.pl bib === id = cord-298604-tn8hc6jv author = Khawaja, Akif A. title = Identification of a Novel HIF-1α-α(M)β(2) Integrin-NET Axis in Fibrotic Interstitial Lung Disease date = 2020-10-15 pages = extension = .txt mime = text/plain words = 7971 sentences = 420 flesch = 40 summary = Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. We measured neutrophil adhesion to primary human endothelial cells in the absence or presence of PMA (a general integrin activator) or LPS (to mimic infectious stimuli), stimuli that induce NETs via distinct pathways (42) . We report, for the first time, that neutrophils and endothelial cells in ILD lung biopsies display HIF-1α expression and provide evidence of the extracellular release of nuclear DNA, citrullinated histones and MPO, indicative of NET formation in the ILD lung. cache = ./cache/cord-298604-tn8hc6jv.txt txt = ./txt/cord-298604-tn8hc6jv.txt === reduce.pl bib === id = cord-032953-qy4b2l2f author = Picard-Sánchez, Amparo title = Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire date = 2020-09-11 pages = extension = .txt mime = text/plain words = 8218 sentences = 410 flesch = 48 summary = title: Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire The results showed that, fish injected with parasite-specific antibodies (spAbs) became infected with the parasite, but showed lower disease signs and intensity of infection than the other groups, indicating a later establishment of the parasite. 1 https://www.genome.jp/tools-bin/clustalw To study the IgM and IgT repertoire in the fish used as serum donors for passive immunization, cDNA from anterior intestine of SUR and NAI donor fish were used as template in PCR amplifications for each primer combination (F + R). Thus, we studied the IgM and IgT repertoire in the GSB that acted as SUR and NAI serum donors for the passive immunization trial. The repertoire analysis was performed on the anterior intestine, as previous studies revealed that in this particular organ IgM and IgT transcript expression increased upon re-exposure to the parasite in resistant fish (29) . cache = ./cache/cord-032953-qy4b2l2f.txt txt = ./txt/cord-032953-qy4b2l2f.txt === reduce.pl bib === id = cord-267237-wbwlfx7q author = Gómez-Rial, Jose title = Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology date = 2020-09-23 pages = extension = .txt mime = text/plain words = 2589 sentences = 148 flesch = 40 summary = METHODS: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. CONCLUSIONS: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. In this paper, we analyze serum levels of soluble monocyte activation markers in COVID-19 patients and their correlation with severity and other inflammatory markers. We found significant correlations between sCD14 and sCD163 levels and several clinical laboratory parameters in infected patients (in these analysis, adjusted significance under Bonferrori correction is 0.01), but only in the non-ICU group, possibly reflecting an interference of the use of tocilizumab or corticoids in the ICU group. Our results thus suggest that monocyte-macrophage activation can act as driver cells of the cytokine storm and immunopathology associated to severe clinical course of COVID-19 patients. cache = ./cache/cord-267237-wbwlfx7q.txt txt = ./txt/cord-267237-wbwlfx7q.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-262944-9k64f0tw author = Parker, Elaine L. title = Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date = 2020-10-07 pages = extension = .txt mime = text/plain words = 9814 sentences = 497 flesch = 43 summary = In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. We will focus on the viruses human Cytomegalovirus (HCMV) and ZIKV, which are known causes of adverse pregnancy outcomes and delve into how they interact with various decidual immune cells to promote their survival and replication. We will explore further the role that NK cells play in specific viral infections in pregnancy TORCH PATHOGENS HCMV Human cytomegalovirus (HCMV) was first described in 1954 by Margaret Smith, who replicated a virus from two newborn babies who had died from cytomegalic inclusion disease (CID) (41) . A study performed using decidual and chorionic villous tissue from early and mid-gestation human pregnancy shows that ZIKV appears to elevate type I and III IFN expression, which does not occur in HCMV infection (131) . cache = ./cache/cord-262944-9k64f0tw.txt txt = ./txt/cord-262944-9k64f0tw.txt === reduce.pl bib === id = cord-279105-e2zjxjox author = Lee, Cheryl Yi-Pin title = Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date = 2020-04-24 pages = extension = .txt mime = text/plain words = 3872 sentences = 212 flesch = 44 summary = With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection. cache = ./cache/cord-279105-e2zjxjox.txt txt = ./txt/cord-279105-e2zjxjox.txt === reduce.pl bib === id = cord-282336-zvc04s39 author = Choudhary, Ishita title = Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date = 2020-09-02 pages = extension = .txt mime = text/plain words = 7910 sentences = 405 flesch = 48 summary = In contrast, the lung injury in LPS-challenged TTP KO mice was characterized by severe consolidation (>90% of total area of lung section) (Figures 1F,G) that included infiltration of neutrophils, edema, fibrin, and airspace hemorrhage within the airway and alveolar lumen, multifocal loss of bronchiolar epithelium with infiltration of neutrophils and red blood cells within the bronchiolar lumen, and moderate to severe perivascular edema and inflammation (Figures 1F-H) . To determine the cell-specific role of TTP levels in ALI, we modulated TTP levels in hematopoietic progenitor cells (HPCs) and non-HPCs. In order to test whether donor HPCs repopulate the recipient mouse lungs, we first made bone marrow chimeras in which total body irradiated WT mice were transplanted with HPCs from a mouse expressing green fluorescent protein (GFP) in their somatic cells. cache = ./cache/cord-282336-zvc04s39.txt txt = ./txt/cord-282336-zvc04s39.txt === reduce.pl bib === === reduce.pl bib === id = cord-034310-izpt032p author = Chernomordik, Fernando title = The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification date = 2020-10-06 pages = extension = .txt mime = text/plain words = 5966 sentences = 306 flesch = 46 summary = Furthermore, studies in apoE−/− mice suggest that T cells reactive to mCRAMP are functionally active in atherosclerosis and may be involved in modulating plaque calcification. Given the role of anti-microbial peptides as potential selfantigens in atherosclerosis, and the possible association with acute events, we tested if the cleaved fragment of hCAP-18, the cationic antimicrobial peptide LL-37, would induce differential T cell immune responses in patients with ACS. In this study, we showed that: (a) LL-37 stimulation of PBMCs from patients with ACS induced the persistence of CD8+ TEM cell response compared to patients with stable CAD or selfreported controls; (b) Immunization of apoE−/− mice with mCRAMP, the cationic fragment of CRAMP, increased CD8 CM T cell activation and cytolytic activity; and (c) Adoptive transfer of T cells from mice immunized with mCRAMP was associated with smaller atherosclerotic aortic plaque area, and absence of aortic sinus plaque calcification. cache = ./cache/cord-034310-izpt032p.txt txt = ./txt/cord-034310-izpt032p.txt === reduce.pl bib === id = cord-268438-bjs5oliw author = Jin, Yilin title = Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination date = 2019-12-03 pages = extension = .txt mime = text/plain words = 5040 sentences = 321 flesch = 51 summary = title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. In the present study, zebrafish TRIM25 (zbTRIM25) was involved in RGNNV infection and was identified as a positive mediator of RLR signaling pathway by binding to and ubiquitinating the caspase activation and recruitment domain (2CARD) and repressor domain (RD) regions of RIG-I, which is different with the findings in mammals. In mammals, previous reports showed that TRIM25 enhanced RLRs antiviral pathway by binding viral RNA-activated RIG-I to induce its K63-linked polyubiquitination and subsequent IFNs and ISGs production (26) . Here, we found that zbTRIM25 positively regulated RLR signaling pathway and facilitated zbRIG-I-mediated IFN 1 promoter activation, and overexpression of zbTRIM25 inhibited RGNNV infection, indicating the conservative antiviral properties of TRIM25 in fish and mammals. cache = ./cache/cord-268438-bjs5oliw.txt txt = ./txt/cord-268438-bjs5oliw.txt === reduce.pl bib === id = cord-256998-or73in8m author = Nguyen, Khue G. title = Localized Interleukin-12 for Cancer Immunotherapy date = 2020-10-15 pages = extension = .txt mime = text/plain words = 26912 sentences = 1416 flesch = 37 summary = Among the more notable responses in other early preclinical studies, nearly half of mice bearing established B16F10 melanomas experienced complete tumor regression following 2 weekly treatments with pIL-12+EP (124) . In preclinical studies, a single intratumoral injection of mRNA encoding murine IL-12 (mIL-12) increased IFNγ expression and genes associated with a Th1 response in MC38 tumor-bearing mice (190) . In a useful comparison against other cytokines, one study demonstrated that Ad-IFN-γ had no greater antitumor activity than an empty Ad vector, whereas AdmIL-12 induced complete regressions of P815 mastocytomas in >80% of treated mice (219) . Antitumor activity on xenografts of human lung tissues indicated that liposomal encapsulation is a promising approach capable of eliminating tumor cells and inducing lymphocyte infiltration 2 weeks after i.t. injection. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8 + T-cell immunity and NK activity cache = ./cache/cord-256998-or73in8m.txt txt = ./txt/cord-256998-or73in8m.txt === reduce.pl bib === id = cord-254192-86ksgl5t author = Li, Liang title = IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia date = 2019-10-17 pages = extension = .txt mime = text/plain words = 7233 sentences = 324 flesch = 50 summary = Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In this study, we comprehensively compared the transcriptional profiling of IFN-λ3-and IFN-α-induced genes in a porcine intestinal epithelial cell line (IPEC-J2) and verified the RNA-Seq results by reverse transcriptase quantitative PCR (RT-qPCR) in vitro, and further confirmed the transcriptional profile difference in crypt-derived porcine enteroids. cache = ./cache/cord-254192-86ksgl5t.txt txt = ./txt/cord-254192-86ksgl5t.txt === reduce.pl bib === id = cord-265855-zf52vl11 author = Mayor-Ibarguren, Ander title = A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection date = 2020-07-10 pages = extension = .txt mime = text/plain words = 5324 sentences = 283 flesch = 47 summary = Zinc deficiency may increase ACE-2 receptor activity on type 2 pneumocytes and other cells that are infected by SARS-COV-2, mainly in the lower respiratory tract. Although there are no specific data regarding zinc in this pathway for SARS-CoV-2, zinc may limit infection through upregulation of IFN-alpha production and an increase in its antiviral activity (77, 78) . Thus, patients with IL-6-174 GG polymorphism (C-carriers) may be susceptible to developing a severe infection due to SARS-CoV-2, leading to an increase in IL-6 levels that produce a cytokine storm related to impaired zinc homeostasis. We believe there is enough evidence to further investigate how zinc status or homeostasis is involved in the pathogenesis of severe illness produced by SARS-CoV-2 infection, and its potential role as an active treatment should be assessed in clinical trials. cache = ./cache/cord-265855-zf52vl11.txt txt = ./txt/cord-265855-zf52vl11.txt === reduce.pl bib === id = cord-003724-705h5l06 author = Di Lullo, Giulia title = Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris date = 2019-06-19 pages = extension = .txt mime = text/plain words = 4132 sentences = 191 flesch = 38 summary = Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The existence of both pathogenic and non-pathogenic anti-Dsg autoAbs has recently been underscored by isolation of human monoclonal antibodies (hMabs) from pemphigus patients. Then, considering that previous studies demonstrated the ability of intact autoAbs to enter living cells (8, 16, 17) , we addressed the potential pathogenicity of α-catenin-specific Mab PVF144 by evaluating its acantholytic activity in an in vitro keratinocyte dissociation assay. Further studies are needed: (i) to evaluate whether PVF144 may act synergistically with anti-Dsg antibodies using more informative approaches, such as in vitro organ culture or in vivo models; (ii) to assess the possible role of anti-α-catenin autoAbs in pemphigus initiation and evolution in vivo; and (iii) to characterize this novel antigen as a possible target of epitope spreading phenomena in PV. cache = ./cache/cord-003724-705h5l06.txt txt = ./txt/cord-003724-705h5l06.txt === reduce.pl bib === === reduce.pl bib === id = cord-268483-joiajgs4 author = Shah, Vibhuti Kumar title = Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date = 2020-08-07 pages = extension = .txt mime = text/plain words = 10644 sentences = 477 flesch = 43 summary = As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. An ELISA-based time kinetics study to detect the COVID-19 specific humoral immune response showed that the patients produced IgM and IgG antibodies that did not cross-react with other human coronaviruses except SARS-CoV. A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65) . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice cache = ./cache/cord-268483-joiajgs4.txt txt = ./txt/cord-268483-joiajgs4.txt === reduce.pl bib === id = cord-263141-n200x6z1 author = Zelaya, Hortensia title = Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection date = 2016-12-23 pages = extension = .txt mime = text/plain words = 8198 sentences = 372 flesch = 30 summary = Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Then, our studies were the first in demonstrating a beneficial modulation of the immune-coagulative response during respiratory TRL3 activation and IFV infection induced by immunobiotic microorganisms (Figure 3) . cache = ./cache/cord-263141-n200x6z1.txt txt = ./txt/cord-263141-n200x6z1.txt === reduce.pl bib === id = cord-254809-o454k6ae author = He, Bing title = The Metabolic Changes and Immune Profiles in Patients With COVID-19 date = 2020-08-28 pages = extension = .txt mime = text/plain words = 4761 sentences = 276 flesch = 60 summary = Third, according to an analysis of nearly 45,000 confirmed cases, 19% of patients with COVID-19 have been identified as severe cases and critically ill cases, involving severe pneumonia and metabolic disorders, developing into acute respiratory distress syndrome (ARDS), multiple organ dysfunctions (MODS), and even septic shock and death (9, 12) . In this study, we investigated mild cases and severe cases infected with SARS-CoV-2, as well as healthy young children and adults. Our study suggests that monocytes, neutrophils, and T-lymphocytes are associated with the onset and progress of COVID-19 infection, and immunopathogenesis was involved in ARDS, metabolic disorders, and MODS in severe cases. We collected the data of patients with COVID-19, including the clinical records, laboratory results and chest computed tomography (CT) scan images of mild and severe cases in the hospital. Extremely high levels of circulating lymphocytes and monocytes would benefit to fight against SARS-CoV-2 infection, which might be associated with the low morbidity of COVID-19 in young children. cache = ./cache/cord-254809-o454k6ae.txt txt = ./txt/cord-254809-o454k6ae.txt === reduce.pl bib === id = cord-269170-9f460xbq author = Kaneko, Kazunari title = Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota date = 2020-07-24 pages = extension = .txt mime = text/plain words = 4597 sentences = 248 flesch = 35 summary = The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This perspective is illustrated in Figure 1 and can be explained as follows: [1] various factors during the in utero and postnatal period drive dysbiosis in young children; [2] dysbiosis results in reduced intestinal production of SCFAs including butyrate; [3] reduced levels of SCFAs in the gut cause an imbalance of Th17s/Tregs; and [4] individuals with Th17/Treg imbalances develop hypercytokinemia triggered by ubiquitous infectious agents(s), followed by KD (Figure 1) . cache = ./cache/cord-269170-9f460xbq.txt txt = ./txt/cord-269170-9f460xbq.txt === reduce.pl bib === id = cord-003685-jcvrqeew author = Gelain, Maria Elena title = Acute Phase Proteins in Marine Mammals: State of Art, Perspectives and Challenges date = 2019-05-29 pages = extension = .txt mime = text/plain words = 4630 sentences = 207 flesch = 37 summary = The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp). To examine the humoral response, species-specific antibodies against IgG were produced and used to evaluate serum IgG levels in killer whale by radial immunodiffusion assay (41) and by competitive ELISA in bottlenose dolphins (42, 43) . Serum total protein analysis were used to assess health status in several cetaceans species such as pantropical spotted dolphins (Stenella attenuata) (48), beluga (49) , minke whales (Balaenoptera acutorostrata) (50) and killer whales (51) as well as in other marine mammals, like harbor seals (Phoca vitulina) (52) and walruses (Odobenus rosmarus) (53) . The availability of sensitive markers of inflammation both for free-ranging and managed marine mammals is nowadays considered fundamental to evaluate the health status and, in rehabilitation setting, to monitor the response to therapy and to define the prognosis. cache = ./cache/cord-003685-jcvrqeew.txt txt = ./txt/cord-003685-jcvrqeew.txt === reduce.pl bib === id = cord-252568-b8sbvy0g author = Marques Neto, Lázaro Moreira title = Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date = 2017-03-08 pages = extension = .txt mime = text/plain words = 5317 sentences = 260 flesch = 39 summary = There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. However, many NPs have been shown to stimulate immune responses, including cell recruitment, activation of antigen (Ag)-presenting cells (APCs), and induction of cytokine and chemokine release. Among the vaccines targeting extracellular bacteria and toxin, two were formulated with lipopolysaccharide (LPS) in glycopeptide Ag. The use of glycoantigen and LPS can trigger an intense response through TLR4 and B cell receptor activation; the presence of gold NPs (AuNPs) may have minimal influence on this response. To understand the possible uses of MeNPs as platforms for vaccines against infectious diseases, analysis is needed of the impact of different physicochemical characteristics of NPs on the innate immune response (Figure 1) . cache = ./cache/cord-252568-b8sbvy0g.txt txt = ./txt/cord-252568-b8sbvy0g.txt === reduce.pl bib === id = cord-260452-js4nr4d8 author = Yu, Junyang title = Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection date = 2017-10-31 pages = extension = .txt mime = text/plain words = 4082 sentences = 222 flesch = 34 summary = Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. IL-1β and IL-18 serve to activate myriad downstream cell responses, and orchestrate innate and adaptive immunity through MyD88/IRAK4/TRAF6-mediated NF-κB signaling and the JNK/p38 mitogen-activated protein kinase pathways (60-63), which may represent key events for the NLRP3 inflammasome-dependent antiviral defense. In BV-2 mouse microglia cells infected by Japanese encephalitis virus, the NLRP3 inflammasome induces production of IL-1β and IL-18 rapidly (within 3 h of exposure) and of TNF-α, CCL2, and IL-6 later (within 6 h after exposure) (40) ; the findings suggest that the NLRP3dependent protective inflammatory response is a very early phase innate immune response against RNA viral infection. cache = ./cache/cord-260452-js4nr4d8.txt txt = ./txt/cord-260452-js4nr4d8.txt === reduce.pl bib === id = cord-280924-g6062fwk author = Hachim, Mahmood Yaseen title = Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date = 2020-06-10 pages = extension = .txt mime = text/plain words = 2851 sentences = 147 flesch = 42 summary = title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. To effectively address the ongoing COVID-19 pandemic, there is a recognized need for a framework for rapid identification of novel targets for diagnostic and therapeutic interventions as well as determine clinically approved drugs with high potential for repurposed use against SARS-CoV-2. In this study, we have applied this approach, and our findings have identified IFITM3 as an early upregulated gene and indicate that valproic acid enhances IFITM3 mRNA expression and antiviral action. Our toxicogenomic analysis showed that valproic acid increased the mRNA expression of IFITM3, supporting a new report that the SARS-CoV-2-human protein-protein interaction map showed that valproic acid might be a potential repurposing drug for COVID-19 (34) . cache = ./cache/cord-280924-g6062fwk.txt txt = ./txt/cord-280924-g6062fwk.txt === reduce.pl bib === id = cord-268511-dx2cqqt5 author = Kunkl, Martina title = CD28 Autonomous Signaling Orchestrates IL-22 Expression and IL-22-Regulated Epithelial Barrier Functions in Human T Lymphocytes date = 2020-10-14 pages = extension = .txt mime = text/plain words = 6320 sentences = 330 flesch = 49 summary = We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. However, although IL-6 itself is able to prime IL-22 production in activated human CD4 + T cells (41) , stimulation of CD4 + T cells with IL-6 alone is not sufficient for up-regulating IL-22 gene expression ( Figure 1G ) but requires a second signal delivered by CD28. During CD28 stimulation, RelA/NF-kB and IL-6-associated STAT3 cooperate for inducing IL-22 expression and secretion ( Figure 3 ) that in turn acts on epithelial cells by promoting the up-regulation of MUC1 ( Figure 4) . cache = ./cache/cord-268511-dx2cqqt5.txt txt = ./txt/cord-268511-dx2cqqt5.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-283505-ousbar6c author = Horman, William S. J. title = The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date = 2020-09-24 pages = extension = .txt mime = text/plain words = 5896 sentences = 266 flesch = 45 summary = To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. In this study, we aimed to examine the ferret immune response to H7N9 influenza virus infection by analyzing leukocyte population variation associated with disease pathogenesis. While the day 6 ferret which showed worsened disease progression did exhibit the most severe lung pathology, the lack of viral antigen in and around these lesions (Supplementary Figure 1) means they cannot conclusively be classified as being caused by the influenza infection, and thus we are hesitant to classify disease presentation in this ferret as like a high pathogenicity infection based on the histopathology findings regardless of the increase in clinical signs. Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses cache = ./cache/cord-283505-ousbar6c.txt txt = ./txt/cord-283505-ousbar6c.txt === reduce.pl bib === id = cord-278081-tk7vn1v1 author = Brooks, Wesley H. title = Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date = 2017-11-28 pages = extension = .txt mime = text/plain words = 9823 sentences = 457 flesch = 42 summary = Here is presented new details to the hypothesis, explaining how the disrupted chromatin can lead to subsequent disruption of the nucleolus, even nucleolar fragmentation, which results in ineffective nucleolar functioning, misfolded RNAs, misassembled or incompletely assembled ribonucleoprotein (RNP) complexes, and stabilization of nucleolar components in autoantigenic conformations. For now there is no direct connection between viruses and the "X chromosome-nucleolus nexus" hypothesis to the increased risk of cancers among autoimmune disease patients but we can consider the induction by viruses of increased polyamine levels and the possible reactivation of X-linked polyamine genes as means by which competition for the cellular methyl donor, SAM, could reduce DNA methylation and open oncogenes for overexpression in proliferation competent cells. A disrupted Barr body could generate an abundance of polyamines and Alu RNA from X-linked genes and elements that further stress and damage the nucleolus, making it very inefficient in its functions, even fragmenting it and possibly leading to cell death. cache = ./cache/cord-278081-tk7vn1v1.txt txt = ./txt/cord-278081-tk7vn1v1.txt === reduce.pl bib === === reduce.pl bib === id = cord-284867-p4jgyusp author = Schöler, Lara title = A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date = 2020-10-09 pages = extension = .txt mime = text/plain words = 4328 sentences = 235 flesch = 42 summary = Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. The fact that the infection and the resulting icELISA signal were neutralized by NAbs present in immune sera indicated that the fast and automated icELISA format is applicable for icNTs. Although most SARS-CoV-2 NTs have not been formally validated and certified, classic plaque reduction neutralization tests (PRNT) are currently considered to represent the gold standard for the detection of SARS-CoV-2-specific NAbs. Various commercially available IgM, IgA, and IgG ELISAs have been compared to PRNTs [e.g., (30) ]. Given the excellent signal-to-noise ratio between infected and uninfected cells, the test was applicable to quantify the efficacy of antiviral compounds, here shown for IFNb, and SARS-CoV-2-specific NAbs present in immune sera. cache = ./cache/cord-284867-p4jgyusp.txt txt = ./txt/cord-284867-p4jgyusp.txt === reduce.pl bib === id = cord-003914-ss8vdpox author = Wang, Shenghua title = Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection date = 2019-10-02 pages = extension = .txt mime = text/plain words = 4829 sentences = 229 flesch = 48 summary = title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection plantarum) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed. plantarum group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection. The ALV-J-NX0101 strain, pMD18T-env recombinant vector (containing the gp85 gene), gp85-specific mouse monoclonal anti-body (MAb JE9), ALV-J antibody test kit, and ALV P27 antigen enzyme-linked immunosorbent assay (ELISA) test kits (IDEXX USA Inc., Beijing, China) were donated by Prof. plantarum significantly triggered specific IgG and IgA antibodies against ALV-J, and enhanced the levels of IgG and sIgA compared to the control group (Figures 4, 5) . This study described the mucosal and systemic immune responses specific to ALV-J induced by an orally administered recombinant L. cache = ./cache/cord-003914-ss8vdpox.txt txt = ./txt/cord-003914-ss8vdpox.txt === reduce.pl bib === id = cord-256582-x2grfhov author = Sung, Pei-Shan title = CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections date = 2019-12-06 pages = extension = .txt mime = text/plain words = 5211 sentences = 237 flesch = 35 summary = Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). Among these Sykcoupled C-type lectins, activation of CLEC5A by flaviviruses and influenza virus induces the production of inflammatory cytokines and NETosis, while these viruses also activate CLEC2 in platelets to elease extracellular vesicles (EVs), which further enhance inflammatory cytokine release and NETosis via CLEC5A and TLR2 in macrophages and neutrophils. Thus, blockade of CLEC5A-mediated signaling in DV infected cells provides a promising strategy for attenuating systemic vascular leakage and increasing the survival rate of patients suffering from DHF/DSS; this approach might also be applicable to other virus-induced inflammatory diseases (1). These viruses are captured by high affinity receptors (DC-SIGN and MR) to induce inflammatory cytokine release via activation of CLEC5A and CLEC2. Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2 cache = ./cache/cord-256582-x2grfhov.txt txt = ./txt/cord-256582-x2grfhov.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-278839-uu2wlpmp author = Alberca, Ricardo Wesley title = Pregnancy, Viral Infection, and COVID-19 date = 2020-07-07 pages = extension = .txt mime = text/plain words = 7237 sentences = 368 flesch = 43 summary = In 2009, during the H1N1 flu pandemic, an increased ratio of female to male cases was verified, in which pregnant women developed more complications, as severe acute respiratory syndrome, and higher mortality compared to the general population (30, 31) . Additionally, infection by the Lassa virus in pregnant women shows high levels of placental replication, and the risk of maternal-fetal mortality increases with the duration of pregnancy (38, 39) . At first, contagion occurred through contact with some infected animals but, soon there were the first reports of human-to-human transmission (93), The virus was identified as belonging to the coronaviridae family and was designated SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) (94). Chen and collaborators, verified alteration in calcium and albumin levels in the blood of pregnant women with SARS-CoV-2 infection (124) , which could potentially increase the severity in COVID-19 (125) . cache = ./cache/cord-278839-uu2wlpmp.txt txt = ./txt/cord-278839-uu2wlpmp.txt === reduce.pl bib === === reduce.pl bib === id = cord-266085-914y3je0 author = Correa, Isabel title = Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells date = 2018-03-23 pages = extension = .txt mime = text/plain words = 6893 sentences = 282 flesch = 42 summary = To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. In our study, we present an antigen-conjugated fluorescent bead methodology designed to identify and isolate single antibody-expressing cells and to derive and clone matched heavy and light chain antibody variable regions into full length antibodies. The workflow features bead-based identification and isolation of specific B cells using direct fluorescent-activated cell sorting, sequencing, and cloning of matched heavy and light chain variable regions in a single full sequence antibody expression vector system, and expression and testing the antigenic reactivity of the antibody clone. Following flow sorting of single cells directly into lysis buffer, we confirmed that it is possible to extract matched H and L chain variable region sequences from single antibody-expressing cells selected by specific antigen-coated beads. cache = ./cache/cord-266085-914y3je0.txt txt = ./txt/cord-266085-914y3je0.txt === reduce.pl bib === === reduce.pl bib === id = cord-291941-9a4tt4f7 author = Barber-Axthelm, Isaac M. title = Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection date = 2020-08-18 pages = extension = .txt mime = text/plain words = 5258 sentences = 252 flesch = 43 summary = Herein, we discuss the current state of MAIT cell characterization in NHPs [which has focused on rhesus macaques (RM), pigtail macaques (PTM), and Mauritian cynomolgus macaques (MCM)] and the changes in MAIT cell populations that occur during simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infection, which are the critical animal models for HIV infection. MAIT cells are consistently maintained at low frequencies in secondary lymphoid organs (lymph nodes and spleen) compared to the peripheral blood, in both humans and NHPs. This is attributed to the relative lack of CCR7 and CD62L expression, both required for lymphoid tissue homing, on peripheral MAIT cells [reviewed in Kurioka et al. The lack of MAIT cell depletion during acute infection is consistent with what has been observed in humans during initial HIV infection and emphasizes the importance of the NHP-SIV/SHIV model to study MAIT cell dynamics during peracute infection. cache = ./cache/cord-291941-9a4tt4f7.txt txt = ./txt/cord-291941-9a4tt4f7.txt === reduce.pl bib === id = cord-263433-oldy0gta author = Barriocanal, Marina title = Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin date = 2015-01-09 pages = extension = .txt mime = text/plain words = 8773 sentences = 497 flesch = 50 summary = As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. To address the issue of whether IFN could also regulate expression of lncRNAs, which may play key roles in the antiviral response, we analyzed the transcriptome of cells treated or not with IFNα2 by RNA sequencing (RNASeq). The results showed that at later times post-infection with the influenza virus lacking NS1, there was increased expression of lncISG15, lncBST2/BISPR, and their neighboring coding transcripts (Figure 3A) . To discriminate whether lncISG15 and lncBST2/BISPR are induced directly by the JAK/STAT signaling pathway or by a secondary wave of the IFN response, we evaluated the expression of these lncRNAs and their coding neighboring genes in HuH7 or A549 cells incubated or not with the JAK/STAT inhibitor ruxolitinib. cache = ./cache/cord-263433-oldy0gta.txt txt = ./txt/cord-263433-oldy0gta.txt === reduce.pl bib === === reduce.pl bib === id = cord-264814-v4wnmg03 author = Flanagan, Katie L. title = Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date = 2020-10-02 pages = extension = .txt mime = text/plain words = 15130 sentences = 700 flesch = 44 summary = Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. cache = ./cache/cord-264814-v4wnmg03.txt txt = ./txt/cord-264814-v4wnmg03.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-295302-vwrxentv author = Shivarov, Velizar title = Potential SARS-CoV-2 Preimmune IgM Epitopes date = 2020-04-30 pages = extension = .txt mime = text/plain words = 2397 sentences = 118 flesch = 50 summary = While studying the human public IgM igome as represented by a library of 224,087 linear mimotopes, three exact matches to peptides in the proteins of SARS-CoV-2 were found: two in the open reading frame 1ab and one in the spike protein. For the present study, the degrees of the vertices representing the natural SARS-CoV-2 epitopes, all of which belonged to the giant component, were used as the number of adjacent mimotopes parameter. A simple comparison for exact matches to peptides from the SARS-CoV-2 proteome yielded 3 heptapeptides-two in the open reading frame 1ab ( 3518 AQTGIAV 3524 and 5198 TKGPHEF 5204 ) and one in the spike protein ( 108 TTLDSKT 114 ). This loop is adjacent to the loop representing the epitope of the neutralizing antibody LCA60 on the SARS-CoV spike (8, 9) . Thus, it is quite possible that the SARS-CoV-2 spike epitope TTLDSKT is bound by B cells that will contribute to the induced immune response. cache = ./cache/cord-295302-vwrxentv.txt txt = ./txt/cord-295302-vwrxentv.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-300429-b0zev8zb author = Sobocińska, Justyna title = Protein Palmitoylation and Its Role in Bacterial and Viral Infections date = 2018-01-19 pages = extension = .txt mime = text/plain words = 13428 sentences = 587 flesch = 40 summary = We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. Given the large variety of chemical reporters preferentially mimicking distinct fatty acids, recent years have witnessed a plethora of chemistry-based proteomic studies not only on palmitoylated but also myristoylated proteins and proteins bearing the GPI anchor, including those of pathogens and immune cells (10, 14, 85, 86, 114) The aBe Method Reveals Protein The envelope is rich in transmembrane, often S-palmitoylated, glycoproteins called spikes, which can bind to cognate receptors on the host cell plasma membrane triggering endocytosis of the virion, mediate subsequent fusion of the viral and cellular membranes allowing entry of the viral genome to the cytoplasm, and are also involved in the budding of newly formed virus particles from the cell. cache = ./cache/cord-300429-b0zev8zb.txt txt = ./txt/cord-300429-b0zev8zb.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-304623-j9ay4jkf author = Entrican, Gary title = The Veterinary Immunological Toolbox: Past, Present, and Future date = 2020-07-28 pages = extension = .txt mime = text/plain words = 5541 sentences = 252 flesch = 33 summary = We review the past, present and future of the veterinary immunological toolbox with specific reference to recent developments discussed at the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) Immune Toolkit Workshop at the 12th International Veterinary Immunology Symposium (IVIS) in Seattle, USA, 16–19 August 2019. The success of the HLDA workshops was based on good co-ordination, high-quality work and collective effort by the veterinary immunology community, as well as results from past species-specific CD workshops supported by IUIS VIC. A barrier to formal international collaboration was lifted in 2013 when USDA/NIFA and BBSRC launched a pilot call to support animal disease research of strategic importance to both the US and UK which included the development of veterinary immunological reagents for agriculturally-relevant animal species. To date, the concept of the veterinary immunological toolbox has largely (but not exclusively) focused on reagent development for livestock species due to their strategic relevance for funders with a stake in livestock health, food safety and global food security. cache = ./cache/cord-304623-j9ay4jkf.txt txt = ./txt/cord-304623-j9ay4jkf.txt === reduce.pl bib === id = cord-304619-tpv76833 author = Chatterjea, Devavani title = Teaching Immunology as a Liberal Art date = 2020-07-14 pages = extension = .txt mime = text/plain words = 3322 sentences = 135 flesch = 41 summary = A complex, rapidly evolving biomedical field that is of critical relevance to human health and well-being, immunology provides important and substantive opportunities to practice and teach the central tenets of a liberal arts curriculum. Iteratively learning to read the often dense and technical immunological literature and synthesizing and communicating these findings in their own written and spoken words is both preparation for future work in biomedical fields and a core tenet of a liberal arts education-the importance of listening, reading, speaking, arguing, and writing. However, they also write white papers and reflective essays connecting their learning in immunology to other disciplines, prepare educational materials for community organizations, teach secondary school students and mentor younger peers and, in doing so, practice translating the technical jargon of scientific communication into information that their audiences need and can use. Teaching about our immune systems in integrative, socially relevant ways can help our students make meaningful connections between the content of their learning and the larger global context in which they live. cache = ./cache/cord-304619-tpv76833.txt txt = ./txt/cord-304619-tpv76833.txt === reduce.pl bib === id = cord-306600-cxz8hf9q author = Matarazzo, Laura title = Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia date = 2019-04-09 pages = extension = .txt mime = text/plain words = 6540 sentences = 316 flesch = 34 summary = Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. pneumoniae lung infection, we recently demonstrated that combination treatment with mucosally administered flagellin and an orally or intraperitoneally administered low-dose (i.e., subtherapeutic) antibiotic is more effective than the antibiotic alone (i.e., with a lower bacterial load in the lung, and a lower mortality rate). Our data showed that several antimicrobial peptides (S100A9), cytokines (IL-1β and TNF), and chemokines (CCL20, CXCL1, and CXCL2) that were associated to epithelial responses are also upregulated after the administration of the combination treatment in the post-flu superinfection model, suggesting that the epithelium is also an important flagellin-specific driving force in the lung damaged by viral and bacterial infections. cache = ./cache/cord-306600-cxz8hf9q.txt txt = ./txt/cord-306600-cxz8hf9q.txt === reduce.pl bib === id = cord-304626-ffao7vka author = Mellors, Jack title = Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics date = 2020-07-09 pages = extension = .txt mime = text/plain words = 11744 sentences = 539 flesch = 34 summary = A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. Infected host cells which present viral antigens on the cell surface membrane can activate the classical pathway, as the antigens bind IgM/IgG to induce complement dependent cytotoxicity (CDC). Non-neutralizing antibodies can still bind the viral target with the potential to cross-link with Fc receptors, or activate complement and interact with complement receptors, to enhance viral infection of host cells (241) . Use of the non-neutralizing influenza virus M2 extracellular vaccine in mice required functional C3 to confer protection and induce effective humoral and cell-mediated immune responses (245) . cache = ./cache/cord-304626-ffao7vka.txt txt = ./txt/cord-304626-ffao7vka.txt === reduce.pl bib === id = cord-305936-tdswzj7r author = Freitas, André Ricardo Ribas title = Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil date = 2018-01-08 pages = extension = .txt mime = text/plain words = 4343 sentences = 193 flesch = 39 summary = Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. We analyzed particularly the most predominant variants (AH1N1 and AH3N2) on excess of mortality in the adults and elderly of different age groups in a region with marked seasonality of respiratory diseases in Brazil. Among adults (24-59 years), we observe a large excess of deaths rates during the 2009 pandemic (953 obits), which correspond to 7.1 excess deaths from all causes, and 99 excess mortality from respiratory diseases associated with viral infection in every 100,000 individuals of the age group. Although the elderly are the most vulnerable group to viral respiratory infections, we found relative small excess of deaths in years of circulating AH1N1 pre pandemic (2002 and 2008) . cache = ./cache/cord-305936-tdswzj7r.txt txt = ./txt/cord-305936-tdswzj7r.txt === reduce.pl bib === id = cord-307813-elom30nx author = Yip, Tsz-Fung title = Advancements in Host-Based Interventions for Influenza Treatment date = 2018-07-10 pages = extension = .txt mime = text/plain words = 15075 sentences = 735 flesch = 38 summary = Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. cache = ./cache/cord-307813-elom30nx.txt txt = ./txt/cord-307813-elom30nx.txt === reduce.pl bib === id = cord-312074-0nqmjdek author = Zhong, Jixin title = Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease date = 2015-09-25 pages = extension = .txt mime = text/plain words = 5420 sentences = 253 flesch = 36 summary = Liebler showed that DPP4 inhibition enhances SDF-1/CXCR4 axis and increased the retention of human bone marrow-derived cells in the injured lungs of immune deficient mice by 30% (71) . It has been shown that parathyroid hormone treatment after myocardial infarction improves DPP4 in chemotaxis and cardiovascular disease Frontiers in Immunology | www.frontiersin.org survival and myocardial function with potential involvement of enhanced homing of bone marrow-derived stem cells. demonstrated that parathyroid hormone serves as a DPP4 inhibitor and increases cardiac SDF-1 level, which in turn enhances CXCR4 + bone marrow-derived stem cell homing to ischemic heart and attenuates ischemic cardiomyopathy after infarction (91) . Suppression of DPP4 enzymatic activities by pharmacological inhibitors preserves SDF-1, which results in an enhanced homing of CXCR4 + progenitor cells from bone marrow to infarcted tissues. cache = ./cache/cord-312074-0nqmjdek.txt txt = ./txt/cord-312074-0nqmjdek.txt === reduce.pl bib === id = cord-308433-vrkdtrfz author = Roberts, Ceri A. title = TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date = 2017-02-15 pages = extension = .txt mime = text/plain words = 7283 sentences = 409 flesch = 56 summary = Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. To investigate whether TNF blockade regulates IL-10 expression in different pro-inflammatory cytokine-producing CD4 + T cells, we isolated CD4 + T cells from PB of healthy donors and cocultured the cells with CD14 + monocytes and anti-CD3 mAb (100 ng/ml) in the absence or presence of the anti-TNF mAb adalimumab (1 µg/ml), as previously described (20) . cache = ./cache/cord-308433-vrkdtrfz.txt txt = ./txt/cord-308433-vrkdtrfz.txt === reduce.pl bib === id = cord-313117-0qur0isb author = Gardinassi, Luiz G. title = Immune and Metabolic Signatures of COVID-19 Revealed by Transcriptomics Data Reuse date = 2020-06-26 pages = extension = .txt mime = text/plain words = 3565 sentences = 177 flesch = 35 summary = To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. In addition, our approach also detected increased signals of monocytes (Figure 1B) , dendritic cells ( Figure 1C ) and of the mitochondrial respiratory electron transport chain in SARS-CoV-2 infection (Figure 1A) , suggesting a critical role of metabolic pathways for the immune response of COVID-19 patients. cache = ./cache/cord-313117-0qur0isb.txt txt = ./txt/cord-313117-0qur0isb.txt === reduce.pl bib === id = cord-313227-6zwkfzab author = Scala, Stefania title = Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date = 2020-05-27 pages = extension = .txt mime = text/plain words = 3872 sentences = 202 flesch = 36 summary = Interestingly, in patients infected by SARS-COv-2, there is an increase in IL1β, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (TH1) cell responses, and increased production of T-helper-2 (TH2) immunosuppressive cytokines, such as IL4 and IL10 (18) . Peripheral blood examinations on admission in the majority of patients with COVID-19 displayed lymphopenia, elevated infection-related biomarkers (i.e., procalcitonin, erythrocyte sedimentation rate, serum ferritin, and C-reactive protein) (20) and several elevated inflammatory cytokines (i.e., tumor necrosis factor (TNF)-α, interleukin (IL)-2R and IL-6). Despite markedly reducing virus titers, anti-S-IgG caused lung injury during the early stages of infection, impairing the wound-healing macrophage response and TGF-β production, while promoting pro inflammatory cytokine IL-8, MCP1 production, and inflammatory macrophage accumulation (22) . Another proteasome inhibitor, VR23, possess powerful antiinflammatory activity reducing IL-6 in synovial cells from RA patients, and improving LPS-induced acute lung injury by decreasing neutrophil migration, TNF-α secretion, and tissue inflammation in a mice model (52) . cache = ./cache/cord-313227-6zwkfzab.txt txt = ./txt/cord-313227-6zwkfzab.txt === reduce.pl bib === === reduce.pl bib === id = cord-319774-mkz7z38o author = Hou, Dongni title = High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease date = 2016-08-31 pages = extension = .txt mime = text/plain words = 6126 sentences = 310 flesch = 36 summary = The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. During the past two decades, however, technical advances in high-throughput sequencing (HTS), also known as next-generation sequencing (NGS), along with evolving bioinformatic and statistical tools, have provided a new approach capable of analyzing the immune repertoire at the single sequence level. The depth and comprehensiveness of high-throughput immune repertoire sequencing are greater than ever, and the enormous sequencing data of disease-specific TCR/BCR clones provide great potential for the revealing dynamic changes in clonality during infectious states. Decrease in the overall diversity of the immune repertoire have been observed after various antigen exposures, including HIV, influenza, and human herpes virus, which implies expansion of particular T/B cell clones (67, 88, 92, 93) . Pairing the heavy and light chains as an integrated antibody has been another challenge for HTS-based immune repertoire analysis. cache = ./cache/cord-319774-mkz7z38o.txt txt = ./txt/cord-319774-mkz7z38o.txt === reduce.pl bib === id = cord-319729-6lzjhn8j author = Tian, Bin title = Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway date = 2018-01-19 pages = extension = .txt mime = text/plain words = 7804 sentences = 409 flesch = 50 summary = title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. To assess innate immune responses in astrocytes, cells were infected with DRV or B2c at an MOI of 0.1 and the expression of several proteins involved in the MAVS signaling pathway, namely, RIG-I, p-IRF7, STAT1 and IFIT1 (ISG56), was measured by Western blot. cache = ./cache/cord-319729-6lzjhn8j.txt txt = ./txt/cord-319729-6lzjhn8j.txt === reduce.pl bib === id = cord-317797-h229skaq author = Li, Conglei title = Crosstalk Between Platelets and Microbial Pathogens date = 2020-08-07 pages = extension = .txt mime = text/plain words = 7628 sentences = 409 flesch = 33 summary = For example, thrombocytopenia in children following varicella zoster virus infection first described antigenic mimicry for some microbial pathogens that encompass host generation of crossreactive antibodies to certain glycoproteins (e.g., GPIIIa) on the platelet surface, resulting in accelerated platelet clearance (117) . In addition to the effects on platelet count and function, microbial pathogens impact the host auto-and alloimmune response to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia (ITP), and fetal and neonatal alloimmune thrombocytopenia (FNAIT) (99-101) (Figure 3) . C-reactive protein is markedly upregulated during acute infections and inflammation (178) , and it has been shown that C-reactive protein, via binding to platelet phosphorylcholine residues, enhanced the IgG-mediated phagocytic responses against platelets and thereby thrombocytopenia, which has implications in the pathogenesis of both ITP and FNAIT (123, 124) . cache = ./cache/cord-317797-h229skaq.txt txt = ./txt/cord-317797-h229skaq.txt === reduce.pl bib === id = cord-318418-uqxzds6g author = Inatomi, Takio title = Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition date = 2017-12-22 pages = extension = .txt mime = text/plain words = 4344 sentences = 219 flesch = 46 summary = title: Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan) to improve the health and reproductive performance of PED-infected sows. The aim of the present study was to evaluate the efficacy of the aforementioned probiotic compound mixed with peptide-zinc to improve the health and reproductive performance of PEDinfected lactating sows when administered along with a PED vaccine injection in Japan. Nonetheless, in the present work, probiotics supplementation significantly improved the concentration of total IgA and IgG in the milk of sows than did PED vaccination alone, possibly resulting from stimulation of gut immunity by bacteria in the administered probiotic compound (Figures 5A,B) . cache = ./cache/cord-318418-uqxzds6g.txt txt = ./txt/cord-318418-uqxzds6g.txt === reduce.pl bib === id = cord-321401-w4ne60fn author = Schrumpf, Jasmijn A. title = Impact of the Local Inflammatory Environment on Mucosal Vitamin D Metabolism and Signaling in Chronic Inflammatory Lung Diseases date = 2020-07-10 pages = extension = .txt mime = text/plain words = 10338 sentences = 522 flesch = 39 summary = Evidence for this immunomodulatory and protective role is derived from observational studies showing an association between vitamin D deficiency, chronic airway diseases and respiratory infections, and is supported by a range of experimental studies using cell culture and animal models. Furthermore, recent intervention studies have now shown that vitamin D supplementation reduces exacerbation rates in vitamin D-deficient patients with chronic obstructive pulmonary disease (COPD) or asthma and decreases the incidence of acute respiratory tract infections. Increasing evidence has indicated that vitamin D deficiency is also associated with various other diseases such as cancer, cardiovascular disease, Alzheimer's disease and muscle myopathy, as well as several immune-related diseases such as type 1 diabetes, multiple sclerosis, inflammatory bowel disease (IBD), psoriasis and chronic inflammatory lung diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) (6) (7) (8) (9) . cache = ./cache/cord-321401-w4ne60fn.txt txt = ./txt/cord-321401-w4ne60fn.txt === reduce.pl bib === id = cord-316702-dj2fo8sn author = Vignesh, Ramachandran title = Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date = 2020-09-30 pages = extension = .txt mime = text/plain words = 3250 sentences = 169 flesch = 45 summary = Since many studies from different geographical locations are documenting preexisting immunity to SARS-CoV-2, it will be important to define specificities of these T and B cell immune response carefully to assess their association with COVID-19 disease severity. This preexisting cross-reactive T and B cell immunity to SARS-CoV-2 may have wide implications as this could explain differential clinical outcomes in COVID-19 patients, disease severity, vaccine development, and important in accessing herd immunity for SARS-CoV-2 viral infection/COVID-19 disease. Several studies have provided strong evidence for the importance of SARS-CoV-2 specific CTLs, and T helper cells in mild and moderate patients compared to severe COVID-19 disease (27, 28, (31) (32) (33) . Several studies have provided strong evidence for the importance of SARS-CoV-2specific neutralizing antibodies in association with less disease severity in COVID-19 patients (38, 39) . A recent modelling study has estimated that about one in five individuals worldwide would be at increased risk of severe COVID-19, upon infection with SARS-CoV-2, owing to the underlying conditions. cache = ./cache/cord-316702-dj2fo8sn.txt txt = ./txt/cord-316702-dj2fo8sn.txt === reduce.pl bib === === reduce.pl bib === id = cord-320431-0877trhh author = Frey, Andreas title = More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis date = 2020-04-28 pages = extension = .txt mime = text/plain words = 15225 sentences = 762 flesch = 40 summary = In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Besides this innate "rapid response team, " the polarized epithelium of the human airways is also able to transport and apically release immunoglobulins that carry a J-chain (joining chain) by using its poly Ig receptor (pIgR) (145) (146) (147) that is expressed by all non-stratified epithelial cells (Figure 2) . After contact for example with HDM extracts, representing a major source of asthma associated allergens, TLR4 dependent activation of NFκB and protease induced injuries in airway epithelial cells lead to secretion of chemokines and cytokines like thymic stromal lymphopoietin (TSLP), GM-CSF, IL-25, and IL-33 (211) (212) (213) (214) (215) . cache = ./cache/cord-320431-0877trhh.txt txt = ./txt/cord-320431-0877trhh.txt === reduce.pl bib === id = cord-333670-qv1orlv5 author = Mutti, Luciano title = Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate? date = 2020-05-28 pages = extension = .txt mime = text/plain words = 2500 sentences = 123 flesch = 40 summary = In Italy, the possibility of performing autopsies or post-mortem diagnostic studies on suspect, probable, or confirmed COVID-19 cases has been intensively debated (5, 6) ; however, postmortem pathological analysis of COVID-19 patients in China has shown findings consistent with Acute Respiratory Distress Syndrome (ARDS) (7-9) (Figure 1 ). Consistently, recent results indicate that a systemic immune dysregulation that triggers auto-sustaining inflammatory lung damage, causing fatal respiratory-failure and consequent multiorgan-failure, is the main virus-related-death cause in patients who develop SARS-CoV-2 (10). Overall, understanding the role of pro-inflammatory cytokines certainly unravels a new battleground against the lethal clinical effect of CODIV-19 infection; this, along with the identification of a high-risk autoimmune profile, including the genotyping of Class I and II HLA, which have a key role in shaping the anti-viral immune response and Th1/Th2 lymphocyte subset response (Figure 1) , and immune-profiling, could also help to prevent these dangerous evolutions of the disease (29) . cache = ./cache/cord-333670-qv1orlv5.txt txt = ./txt/cord-333670-qv1orlv5.txt === reduce.pl bib === === reduce.pl bib === id = cord-312955-gs65c3fy author = Schreiber, Gideon title = The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date = 2020-09-30 pages = extension = .txt mime = text/plain words = 8418 sentences = 467 flesch = 48 summary = Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Thereby, it inhibits the nuclear transport of phosphorylated STAT1, rendering cells refractory to IFN-Is. Another example of viral mechanisms that evolved to eliminate IFN-I functions in inducing innate immunity is given by the SARS corona virus, where both the production of IFNb and the IFN-I induced signaling are attenuated. This gene was found to preferentially cleave the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), FIGURE 4 | SARS-CoV-2 has multiple effects on the immune system, including inhibition of IFNb production, which results in ISGs not to be produced, CD4+ and CD8+ exhaustion and increased levels of pro-inflammatory proteins (TNFa, IL6, NF-kB). cache = ./cache/cord-312955-gs65c3fy.txt txt = ./txt/cord-312955-gs65c3fy.txt === reduce.pl bib === id = cord-313431-swkcdvx8 author = Becerra-Diaz, Mireya title = Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung date = 2020-08-07 pages = extension = .txt mime = text/plain words = 14972 sentences = 789 flesch = 40 summary = The opposite effects seen in different inflammatory contexts highlight the need for a deeper and broader study of the androgen/ARmediated modulation of monocytes and macrophages, as these cells participate in both the initial and late phases of immune responses in a variety of diseases. Studies of androgen receptor function in human monocytes and macrophages have focused primarily on the roles of male sex and sex hormones in promoting atherosclerotic foam cell formation (196) and inhibiting cutaneous wound healing (186, 215) . There is a paucity of literature regarding how introducing or depleting exogenous sex hormones (such as in female-to-male transgender individuals receiving testosterone supplementation or women with estrogen blockade) affects the function of blood monocytes and lung macrophages in men and women with asthma. Modulation of monocyte and macrophage function mediated by the interaction of androgen and AR has been examined mostly by correlative studies in humans following lifespan changes in sex hormones or using hormonal manipulation in mouse models of lung disease. cache = ./cache/cord-313431-swkcdvx8.txt txt = ./txt/cord-313431-swkcdvx8.txt === reduce.pl bib === id = cord-323756-atnrw9ew author = Vabret, Nicolas title = Sensing Microbial RNA in the Cytosol date = 2013-12-25 pages = extension = .txt mime = text/plain words = 6409 sentences = 355 flesch = 45 summary = When Janeway formulated the theory of pattern recognition in 1989, he proposed that host cells could sense microbial infection owing to receptors able to recognize invariant molecular structures defined as pathogen-associated molecular patterns (PAMPs). They share a similar organization with three distinct domains: (i) a C-terminal repressor domain (RD) embedded within the C-terminal domain (CTD); (ii) a central ATPase containing DExD/H-box helicase domain able to bind RNA; and (iii) a N-terminal tandem CARD domain that mediates downstream signaling, and which is present in RIG-I and MDA5 but absent in LGP2. DDX60 has also been shown to enhance the IFN-I response to RNA and DNA stimulation through formation of complexes with Frontiers in Immunology | Molecular Innate Immunity RIG-I, MDA5, and LGP2 but not with MAVS. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses cache = ./cache/cord-323756-atnrw9ew.txt txt = ./txt/cord-323756-atnrw9ew.txt === reduce.pl bib === id = cord-328003-yovp8squ author = Duan, Liangwei title = The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date = 2020-10-07 pages = extension = .txt mime = text/plain words = 7346 sentences = 386 flesch = 46 summary = Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. cache = ./cache/cord-328003-yovp8squ.txt txt = ./txt/cord-328003-yovp8squ.txt === reduce.pl bib === id = cord-333932-aqcllik0 author = Diao, Bo title = Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) date = 2020-05-01 pages = extension = .txt mime = text/plain words = 3822 sentences = 179 flesch = 50 summary = Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. Our results thus provide a preliminary demonstration of T cell exhaustion during COVID-19 infection and suggest that more urgent, early intervention may be required in patients with low T lymphocyte counts. The expression of angiotensin converting enzyme 2 (ACE2), the predicted receptor of SARS-CoV-2 viruses, is absent on T cells (11) , suggesting that the depressed T counts in COVID-19 patients mentioned above (Figure 1 ) were likely not caused by direct infection of T cells. We demonstrate here that COVID-19 patients have very high levels of serum IL-10 following SARS-CoV-2 infection, while also displaying high levels of the PD-1 and Tim-3 exhaustion markers on their T cells, suggesting that IL-10 might be mechanistically responsible. cache = ./cache/cord-333932-aqcllik0.txt txt = ./txt/cord-333932-aqcllik0.txt === reduce.pl bib === id = cord-340228-mvqoyror author = Al-Herz, Waleed title = Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry date = 2019-05-29 pages = extension = .txt mime = text/plain words = 2930 sentences = 170 flesch = 42 summary = Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The distribution of these patients according to PID categories is: immunodeficiencies affecting cellular and humoral immunity, 97 patients (35.4%); combined immunodeficiencies with associated syndromic features, 67 patients (24.5%); predominantly antibody deficiencies, 34 patients (12.4%); diseases of immune dysregulation, 47 patients (17.2%); congenital defects of phagocyte number or function, 17 patients (6.2%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 11 patients (4%). cache = ./cache/cord-340228-mvqoyror.txt txt = ./txt/cord-340228-mvqoyror.txt === reduce.pl bib === id = cord-332150-j76726no author = De Stefano, Ludovico title = A “Window of Therapeutic Opportunity” for Anti-Cytokine Therapy in Patients With Coronavirus Disease 2019 date = 2020-10-06 pages = extension = .txt mime = text/plain words = 3616 sentences = 166 flesch = 28 summary = The main challenge for effective administration of anti-cytokine therapy in COVID-19 will be therefore to better define a precise "window of therapeutic opportunity." Only considering a more specific set of criteria able to integrate information on direct viral damage, the cytokine burden, and the patient's immune vulnerability, it will be possible to decide, carefully balancing both benefits and risks, the appropriateness of using immunosuppressive drugs even in patients affected primarily by an infectious disease. Discovery of virus and host genomic factors will undoubtedly support risk stratification and targeted treatment; however, as genomic studies require long times before entering clinical practice, it is urgent to integrate easily accessible information on the dynamics and pathogenicity of the immune response during the different phases of SARS-CoV-2 infection. Accordingly, longitudinal immune profiling of hospitalized COVID-19 cases with different outcomes has recently shown that, despite similar levels of inflammatory cytokines in the first 10 days from symptom onset, patients with less severe disease evolution also express mediators of wound healing and tissue repair (41) . cache = ./cache/cord-332150-j76726no.txt txt = ./txt/cord-332150-j76726no.txt === reduce.pl bib === id = cord-328011-6lf3no6u author = Zayed, Hatem title = Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics date = 2020-08-14 pages = extension = .txt mime = text/plain words = 1449 sentences = 84 flesch = 49 summary = title: Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics Since coronaviruses are increasing alarmingly, there is an urgent need for a safe and effective vaccine to prevent the spread of the virus during pandemic outbreaks, and stop deaths associated with the virulent COVID-19. We now know that SARS-CoV-2 shares 88% identity with two SARS-like coronaviruses (bat-SL-CoVZXC21 and bat-SL-CoVZC45) that both originated in China, and use the same human angiotensin-converting enzyme 2 receptor for cell entry during the process of infection (3). In response to such forewarnings from scientists, a predictive vaccine could have been designed and developed for the potential virus pandemic. Thereafter, during the time of pandemic, suitable stored transgenic cell lines could be used, based on the Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VLP, virus-like particle; WHO, World Health Organization. cache = ./cache/cord-328011-6lf3no6u.txt txt = ./txt/cord-328011-6lf3no6u.txt === reduce.pl bib === id = cord-325353-tx6s4ggu author = Restori, Katherine H. title = Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma date = 2018-06-04 pages = extension = .txt mime = text/plain words = 13653 sentences = 618 flesch = 42 summary = The goals of this review are (1) to outline the differences between the neonatal and adult immune systems and (2) to present murine and human data that support the hypothesis that early-life interactions between the immune system and respiratory viruses can create a lung environment conducive to the development of asthma. Because RSV, influenza, and RVs cause a large proportion of respiratorytract infections in neonates, we will focus primarily on these three pathogens as models to better understand how early-life infection and antiviral immune responses might contribute to the subsequent development of asthma. The addition of RSV infection of airway epithelial cells with production of the type-2 innate cytokines, IL-33 (138) , TSLP (123) , and IL-25 (128) , would, therefore, be predicted to create an even more exaggerated type-2-biased microenvironment in the lung with activation of other immune cells (e.g., M2 macrophages, DCs, and/or ILC2 cells) and the development of AHR. cache = ./cache/cord-325353-tx6s4ggu.txt txt = ./txt/cord-325353-tx6s4ggu.txt === reduce.pl bib === id = cord-328549-r56lih8j author = Okamoto, Masaaki title = Regulation of RIG-I Activation by K63-Linked Polyubiquitination date = 2018-01-05 pages = extension = .txt mime = text/plain words = 3618 sentences = 216 flesch = 47 summary = First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. However, recent studies have reported three other ubiquitin ligases, RING finger protein leading to RIG-I activation (Riplet), mex-3 RNA-binding family member C (MEX3C), and TRIM4, which are required for the polyubiquitination and activation of RIG-I (28-30). cache = ./cache/cord-328549-r56lih8j.txt txt = ./txt/cord-328549-r56lih8j.txt === reduce.pl bib === id = cord-318630-h6j7iqbm author = Sinha, Sushmita title = CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis date = 2015-12-10 pages = extension = .txt mime = text/plain words = 9004 sentences = 465 flesch = 50 summary = In our studies, we have shown that cytotoxic/suppressor CD8(+) T-cells are CNS antigen-specific, MHC class I-restricted, IFNγand perforin-dependent, and are able to inhibit disease. iNTRODUCTiON Studies addressing the immunobiology of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) have focused on CD4 + T-cells as the main orchestrators of pathogenesis and regulation. Interestingly, immune deviation can be elicited against myelin antigens (61, 62) , pointing to the potential role for Qa-1-restricted CD8 + T-cells in EAE disease. We have also demonstrated that GA treatment induces CD8 + Treg in mice, and that these CD8 + T-cells are required for GA to be therapeutically effective in ameliorating EAE disease (64) . Furthermore, relapses in MS are associated with significantly lower CNS-specific CD8 + T-cell suppressor ability, while this potential in MS patients during quiescence is similar to healthy donors, suggesting a role with disease activity (5) . cache = ./cache/cord-318630-h6j7iqbm.txt txt = ./txt/cord-318630-h6j7iqbm.txt === reduce.pl bib === id = cord-338261-tyimwctm author = Farr, Laura title = Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair date = 2020-06-23 pages = extension = .txt mime = text/plain words = 5261 sentences = 306 flesch = 39 summary = title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair This mini review focuses on emerging literature on the role of the cytokine macrophage migration inhibitory factor (MIF) and its cell membrane receptor CD74, in protecting against injury and promoting healing in different parts of the body. This review focuses on the recent advances that have greatly contributed to our current understanding of the link between the signaling pathways activated upon binding of macrophage migration inhibitory factor cytokine to its membrane receptor CD74 and wound healing in different body parts (Figure 1 ). The complex pathological processes that result in disease combined with CD74's expression on a variety of cell types, and its multiple co-receptors with diverse downstream signaling pathways contribute to these varied outcomes. Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair cache = ./cache/cord-338261-tyimwctm.txt txt = ./txt/cord-338261-tyimwctm.txt === reduce.pl bib === id = cord-351305-6vtv2xuh author = Schramm, Markus A. title = COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis date = 2020-08-28 pages = extension = .txt mime = text/plain words = 1260 sentences = 64 flesch = 38 summary = The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA). Thus, due to severity and refractory disease the previously healthy patient was continuously hospitalized from January to March 2020, receiving intravenous cyclophosphamide (CYCLOPS-protocol, cumulative dose 4.76 g), rituximab (4 × 375 mg/m 2 ), and a long-term, slowly tapered high-dose prednisolone treatment (up to 1 g/day). Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients cache = ./cache/cord-351305-6vtv2xuh.txt txt = ./txt/cord-351305-6vtv2xuh.txt === reduce.pl bib === id = cord-338498-3238fz73 author = Kleen, Thomas-Oliver title = Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends” date = 2020-09-04 pages = extension = .txt mime = text/plain words = 12523 sentences = 559 flesch = 39 summary = Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends." One recent example of the need for continued vigilance is a study using Chinese macaques indicating cause for concern by showing that vaccine-induced, S-specific immunity in the form of anti-spike IgG resulted in severe ALI by skewing macrophage responses during subsequent, acute infection with closely related SARS-CoV (139) . cache = ./cache/cord-338498-3238fz73.txt txt = ./txt/cord-338498-3238fz73.txt === reduce.pl bib === id = cord-348283-7xorq5ce author = Naz, Anam title = Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach date = 2020-07-10 pages = extension = .txt mime = text/plain words = 8183 sentences = 482 flesch = 56 summary = The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Designed vaccines were then tested with different epitopes, including Truncated Ov-ASP-1 Protein (residues 10-153) and Beta defensin (45 residues long), and constructs having higher antigenicity and that are predicted to produce high antibody titers were added with the multi epitope vaccine construct to the enhance immune response (30) . For the interaction analysis of vaccine 3 and BCR (CD79), the HADDOCK server clustered 140 probable structures into 13 different clusters, which represented a total of 70% of the water-refined models. cache = ./cache/cord-348283-7xorq5ce.txt txt = ./txt/cord-348283-7xorq5ce.txt === reduce.pl bib === id = cord-350492-1s6wtj25 author = Ruscitti, Piero title = Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm date = 2020-05-28 pages = extension = .txt mime = text/plain words = 3728 sentences = 154 flesch = 29 summary = On these bases, we aimed to review the similarities between severe COVID-19 and diseases included in hyperferritinemic syndrome, from a pathogenic, clinical, and therapeutic point of view, thus proposing new insights to improve the management of those patients. In addition, it has been shown that increased amounts of pro-inflammatory cytokines, including IL-1β, IL-6, IL-12, IFN-γ, IP-10, and MCP1, were associated with pulmonary inflammation and extensive lung damage in SARS patients (25) , thus suggesting a further pathogenic loop in inducing the cytokine storm. The final result is the uncontrolled proliferation of activated immune cells, the massive production of pro-inflammatory mediators, and the development of cytokine storm syndrome, either in severe COVID-19 or SJIA. Considering the lack of efficacy of antiviral therapy for severe coronavirus infection, it is reasonable to postulate the clinical usefulness of specific immunomodulatory therapies (Figure 1) , as observed for other diseases included in hyperferritinemic syndrome such as intravenous immunoglobulins (IVIGs) and tocilizumab, the humanized monoclonal antibody against IL-6 receptor (7). cache = ./cache/cord-350492-1s6wtj25.txt txt = ./txt/cord-350492-1s6wtj25.txt === reduce.pl bib === id = cord-344610-mqq6fmsp author = Waumans, Yannick title = The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis date = 2015-08-07 pages = extension = .txt mime = text/plain words = 9097 sentences = 481 flesch = 42 summary = Usually only four prolyl-specific peptidases are considered: DPPIV (EC 3.4.14.5), fibroblast activation protein α (FAP; EC 3.4.21.B28), and the more recently discovered DPP8 and DPP9 (EC 3.4.14). However, due to similarities in substrate specificity and structural homology, it is more relevant to consider a broader family that also includes prolyl oligopeptidase (PREP; EC 3.4.21.26), dipeptidyl peptidase II (DPPII) (EC 3.4.14.2), and prolyl carboxypeptidase (PRCP; EC 3.4.16.2). Three other studies also found no to low DPPIV expression or activity associated with human monocytes and/or macrophages (82, [136] [137] [138] . Dipeptidyl peptidase 4 is present in low amounts on freshly isolated human NK cells and its expression is only upregulated in a small subpopulation after IL-2 stimulation (158) . Dipeptidyl peptidase 8 and 9 have been found to be abundantly present in the macrophage-rich regions of human atherosclerotic plaques and considering DPP9's role in macrophage activation, it might potentially be involved in atherogenesis (82). Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells cache = ./cache/cord-344610-mqq6fmsp.txt txt = ./txt/cord-344610-mqq6fmsp.txt === reduce.pl bib === id = cord-340475-h0q1m3ed author = Carnero, Elena title = Type I Interferon Regulates the Expression of Long Non-Coding RNAs date = 2014-11-06 pages = extension = .txt mime = text/plain words = 10164 sentences = 544 flesch = 55 summary = Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response.These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. HuH7 cells were treated for 6, 24, 48, or 72 h with increasing doses of IFNα2 up to 10,000 units/ml, and the expression levels of GBP1, IRF1, BST2, OAS, IL6, and ISG15 were evaluated by qRT-PCR (Figure 1) . cache = ./cache/cord-340475-h0q1m3ed.txt txt = ./txt/cord-340475-h0q1m3ed.txt === reduce.pl bib === id = cord-344829-adlp2rjy author = de Rivero Vaccari, Juan Carlos title = The Inflammasome in Times of COVID-19 date = 2020-10-08 pages = extension = .txt mime = text/plain words = 8722 sentences = 423 flesch = 37 summary = Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients. Here we review the literature on the role of the inflammasome in CoV infections, which includes how CoVs activate inflammasomes upon infection, the role of the inflammasome in acute respiratory distress syndrome (ARDS), how ventilator-induced lung injury (VILI) activates the inflammasome, how the inflammasome plays a role in the systemic complications associated with COVID-19, and how the inflammasome is involved in the process of Disseminated Intravascular Coagulation (DIC). cache = ./cache/cord-344829-adlp2rjy.txt txt = ./txt/cord-344829-adlp2rjy.txt === reduce.pl bib === id = cord-336924-7xcbtn3q author = Borghi, Maria Orietta title = Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome date = 2020-10-15 pages = extension = .txt mime = text/plain words = 3190 sentences = 185 flesch = 48 summary = OBJECTIVE: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β(2)GPI antibodies. aPL in COVID-19 patients are mainly directed against β(2)GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome. The prevalence of COVID-19 patients positive for aCL and anti-b 2 GPI IgG/IgA/ IgM detected by ELISA and CIA is summarized in Table 2 . Again, there was no association between prolonged aPTT and the presence of aPS/PT antibodies nor with thrombotic events in our COVID-19 cohort. Again, there was no association between prolonged aPTT and the presence of aPS/PT antibodies nor with thrombotic events in our COVID-19 cohort. In conclusion, while the medium/high aPL titers with D1 specificity are associated with vascular events in APS, low antibody titers with reactivity against b 2 GPI epitope(s) different from D1 or D4,5 can be found in COVID-19. cache = ./cache/cord-336924-7xcbtn3q.txt txt = ./txt/cord-336924-7xcbtn3q.txt === reduce.pl bib === id = cord-330417-8nnobx8g author = Herrmann, Marissa title = Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease date = 2020-08-26 pages = extension = .txt mime = text/plain words = 8853 sentences = 399 flesch = 51 summary = Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8 + and CD4 + T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8 + and CD4 + T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. cache = ./cache/cord-330417-8nnobx8g.txt txt = ./txt/cord-330417-8nnobx8g.txt === reduce.pl bib === id = cord-353217-gmc3qrci author = de Miranda Santos, Isabel Kinney Ferreira title = Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus date = 2020-08-04 pages = extension = .txt mime = text/plain words = 551 sentences = 34 flesch = 36 summary = Recent large observational studies indicate that hydroxychloroquine (HY) does not affect outcomes of patients hospitalized with COVID-19 (1, 2) and may even be harmful (3) . In view of this situation and of the importance of correct interpretation of antibody profiles for planning preventive measures for COVID-19, we would like to bring the attention of readers to studies that raise concerns about the possible impact of HY upon antibody responses to SARS-CoV-2. To the best of our knowledge, there are no new facts in the scientific and medical literature that indicate that the same mechanism could not operate in HY-treated patients suffering from COVID-19 and negatively impact their SARS-CoV-2-specific antibody responses. As more needs to be learned about the role of antibodies in recovery from and protection against infection with SARS-CoV-2, the impact of HY and other treatment regimens on antibody responses requires systematic evaluation. cache = ./cache/cord-353217-gmc3qrci.txt txt = ./txt/cord-353217-gmc3qrci.txt === reduce.pl bib === id = cord-341513-e6p3lrlf author = Li, Yunchuan title = Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection date = 2017-09-29 pages = extension = .txt mime = text/plain words = 6136 sentences = 341 flesch = 47 summary = title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection To determine the role of lncRNAs in inflammatory cytokine production, the cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. To examine the role of lncRNA E52329 and N54010 in regulating the kinase activity of MKK4/JNK pathway, BV2 cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. The results of our study reveal the first experimental evidence demonstrating the complex regulation of lncRNAs by JEV infection in mice brain and microglial cells. Third, the integration of microarray platform, quantitative real-time PCR, GO analysis, pathways analysis, and lncRNA-mRNA coexpression network analysis has allowed us to conduct an active comparative genomics and bioinformatics study to reveal host lncRNAs expression patterns associated with JEV infection. cache = ./cache/cord-341513-e6p3lrlf.txt txt = ./txt/cord-341513-e6p3lrlf.txt === reduce.pl bib === id = cord-342776-hkjhqgie author = Jewett, Anahid title = The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions date = 2020-07-10 pages = extension = .txt mime = text/plain words = 3612 sentences = 159 flesch = 41 summary = While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease. In particular, in the peripheral blood of patients that were infected with SARS, it was noted that there were significantly lower numbers of natural killer (NK) cells compared to healthy subjects (14) . As mentioned above the infectious agent of COVID-19 disease depletes NK cells in the peripheral blood, and potentially even in the lung tissues of patients, thereby, disabling and depleting the core immune effectors necessary to remove the virus and regulate uncontrolled immune activation. cache = ./cache/cord-342776-hkjhqgie.txt txt = ./txt/cord-342776-hkjhqgie.txt === reduce.pl bib === === reduce.pl bib === id = cord-333041-69n2wwn3 author = Pal, Anandita title = Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection date = 2020-08-11 pages = extension = .txt mime = text/plain words = 4394 sentences = 227 flesch = 43 summary = Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Obesity is an independent risk factor for increased morbidity and mortality upon infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic. The SPM precursor 17-hydroxydocosahexaenoic acid (17-HDHA) increased antibody levels and improved survival upon pH1N1 influenza vaccination and infection in lean mice by promoting B cell differentiation toward the formation of CD138 + long-lived antibody secreting cells (18) . Taken together, these data suggest that the susceptibility of obese individuals to environmental lung diseases may drive an altered pulmonary immune response and a state of SPM deficiency that increases the morbidity and mortality to respiratory infections, including COVID-19. cache = ./cache/cord-333041-69n2wwn3.txt txt = ./txt/cord-333041-69n2wwn3.txt === reduce.pl bib === id = cord-325129-faptufak author = Meini, Simone title = Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key? date = 2020-08-11 pages = extension = .txt mime = text/plain words = 5501 sentences = 255 flesch = 38 summary = Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. In this review, we try to address the complex link between the pathophysiology of COVID-19 and the different proteolytic defense systems operating in human vasculature, investigating the role of the mediators involved and speculating on the possibility of pharmacological modulation. After binding through its B2R, BK activates signaling pathways resulting in increased vascular permeability, vasodilation, edema formation, hypotension, pain, fever (14) : all typical clinical features of COVID-19. (79) hypothesized that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19 and proposed that blocking the B2R and inhibiting plasma KAL activity might be beneficial in early disease, preventing ARDS. cache = ./cache/cord-325129-faptufak.txt txt = ./txt/cord-325129-faptufak.txt === reduce.pl bib === id = cord-334564-bqh9jkds author = Raony, Ícaro title = Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date = 2020-05-27 pages = extension = .txt mime = text/plain words = 9893 sentences = 464 flesch = 41 summary = Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) . cache = ./cache/cord-334564-bqh9jkds.txt txt = ./txt/cord-334564-bqh9jkds.txt === reduce.pl bib === id = cord-323590-m4jsu1q5 author = Ortiz de Landazuri, Iñaki title = Manufacturing and Management of CAR T-Cell Therapy in “COVID-19’s Time”: Central Versus Point of Care Proposals date = 2020-10-15 pages = extension = .txt mime = text/plain words = 4339 sentences = 230 flesch = 41 summary = The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. Therefore, the aim of this mini-review is to focus on how the effects caused by the pandemic have affected this therapy taking into consideration the differences between the large-scale centralized production of CAR T-cells by the pharmaceutical industry versus the product manufacturing processes employed by the academic/hospital environment. We also review different aspects of CAR T-cell therapy, including patient selection and resource prioritization performed in our center during the COVID-19 pandemic. cache = ./cache/cord-323590-m4jsu1q5.txt txt = ./txt/cord-323590-m4jsu1q5.txt === reduce.pl bib === id = cord-344093-3bniy5b5 author = Peteranderl, Christin title = The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date = 2017-03-22 pages = extension = .txt mime = text/plain words = 12546 sentences = 578 flesch = 34 summary = A prominent regulator of disease outcome, especially in-but not limited to-respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. (73) Cell death induction, e.g., Bcl-2-associated X protein, caspase-8, Fas-associated protein with death domain, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL) dsRNA, polyI:C (4, 110) IAV (4, 5, 10, 115) Sendai virus (110) TRAIL Virus control by apoptosis induction in infected cells IAV (6, 170, 171) Tissue injury by apoptosis of both infected and non-infected alveolar epithelial cells, lung macrophages IAV (5, 7, 10) RSV (137) Necrosis of fibroblasts, dendritic cells, and epithelial cells IAV (146, 147, 168) Increased cellular infiltration CoV (175) Decreased expression of Na,K-ATPase, impaired epithelial fluid reabsorption IAV (11) iNTRODUCTiON In 1957, Isaacs and Lindenmann (1) first recognized the potential of a soluble and probably cell-derived factor to combat influenza virus infection and named this factor interferon [(IFN) from latin interferre, to interfere]. cache = ./cache/cord-344093-3bniy5b5.txt txt = ./txt/cord-344093-3bniy5b5.txt === reduce.pl bib === id = cord-353594-z1vxamvp author = Gagiannis, Daniel title = Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) date = 2020-10-02 pages = extension = .txt mime = text/plain words = 4997 sentences = 246 flesch = 40 summary = Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Patients or their relatives had given written informed consent to routine diagnostic procedures (serology, bronchoscopy, radiology) as well as (partial) autopsy in the case of death, respectively, as well as to the scientific use of data and tissue samples in the present study. Our finding that significant ANA titers and/or detection of specific autoantibodies are found in most patients who develop ARDS raises the question if there is a comparable mechanism of lung damage between SARS-CoV-2 infection and exacerbating autoimmune disease. Our observation of CTD-associated autoantibodies together with the CTD-like radiologic and histopathologic lung findings in severe cases of COVID-19 point towards a possible dysregulation of the immune response upon SARS-CoV-2 infection that might fuel organizing pneumonia and trigger interstitial fibrosis, with deleterious effects on the functional outcome in long-term survivors. cache = ./cache/cord-353594-z1vxamvp.txt txt = ./txt/cord-353594-z1vxamvp.txt === reduce.pl bib === id = cord-320474-jyk7zphp author = Bonaventura, Aldo title = Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies date = 2020-07-03 pages = extension = .txt mime = text/plain words = 5082 sentences = 242 flesch = 38 summary = Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Data supporting the role of hyperinflammation in sepsisrelated acute respiratory distress syndrome (ARDS) are derived from a sub-group analysis of a phase 3 randomized controlled trial of IL-1 receptor antagonist (anakinra), which showed significant survival benefit in patients treated with anakinra compared to placebo (15) . APC, antigen presenting cell; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. A randomized, double-blind, placebo-controlled phase II study tested the effects of low-dose hrGM-CSF (molgramostim, 3 µg/kg daily) for 5 days in patients in addition to the standard of care in critically ill patients with severe sepsis and respiratory dysfunction (65) . cache = ./cache/cord-320474-jyk7zphp.txt txt = ./txt/cord-320474-jyk7zphp.txt === reduce.pl bib === id = cord-352960-pfccsgco author = Gössling, Katharina L. title = Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome date = 2017-06-30 pages = extension = .txt mime = text/plain words = 3292 sentences = 176 flesch = 43 summary = Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous descent diagnosed with ICF syndrome carrying a homozygous missense mutation in the DNMT3B gene (Ala603Thr) with hypogammagobulinemia, normal B cell count, facial anomaly, and failure to thrive. We report the successful allogeneic HSCT of a 1-year-old boy with ICF1 syndrome carrying a homozygous mutation in the DNMT3B gene after receipt of bone marrow cells from the 10/10 HLA-matched clinically healthy sister. cache = ./cache/cord-352960-pfccsgco.txt txt = ./txt/cord-352960-pfccsgco.txt === reduce.pl bib === id = cord-338092-barmkkwx author = Geginat, Jens title = Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets date = 2015-10-13 pages = extension = .txt mime = text/plain words = 8573 sentences = 421 flesch = 45 summary = Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. BDCA-3(+) mDC2 are the human homologue of CD8α(+) mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8(+) T-cells and to produce IFN-λ. Dendritic cells (DCs) can express very high levels of MHC and costimulatory molecules, and it is generally accepted that they are the relevant cells to induce the activation ("priming") of antigen-specific "naive" T cells (1, 2) and induce their differentiation into various types of effector T cells. Overall, these differences in pathogen sensing and T-cell activation between human and murine DCs are likely to have an important impact on their role in immune responses against specific pathogens. Dendritic cell subsets in humans and mice express not only different patterns of toll-like receptors, but they have also partially distinct cytokine profiles (Figure 1) . cache = ./cache/cord-338092-barmkkwx.txt txt = ./txt/cord-338092-barmkkwx.txt === reduce.pl bib === id = cord-340741-bhxm4zua author = Nayak, Tapas Kumar title = P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date = 2019-04-12 pages = extension = .txt mime = text/plain words = 8025 sentences = 394 flesch = 48 summary = title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. In summary, for the first time it has been shown that CHIKV triggers robust TNF production (a key mediator of CHIKV induced inflammation) in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and viral protein nsP2 interacts with both the MAPKs during infection. cache = ./cache/cord-340741-bhxm4zua.txt txt = ./txt/cord-340741-bhxm4zua.txt === reduce.pl bib === id = cord-351431-xcqz9d3t author = Wang, Jun title = Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19 date = 2020-08-18 pages = extension = .txt mime = text/plain words = 4522 sentences = 268 flesch = 48 summary = Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Principal component analysis was performed with R package "FactoMineR" to identify those clinical parameters that contribute most to distinguishing severe, moderate, and mild cases of COVID-19 (28) . For BALF, the most upregulated marker genes were similarly enriched in neutrophils, but more up-regulated genes in monocytes and B cells were observed in COVID-19 patients compared to healthy controls, which is different from the lung samples. Transcriptome analysis of lung specimens and BALF from COVID-19 patients also indicated the most up-regulated marker genes were neutrophil related. Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19 cache = ./cache/cord-351431-xcqz9d3t.txt txt = ./txt/cord-351431-xcqz9d3t.txt === reduce.pl bib === id = cord-354353-hyz0gmpz author = Farhangrazi, Z. Shadi title = Airborne Particulate Matter and SARS-CoV-2 Partnership: Virus Hitchhiking, Stabilization and Immune Cell Targeting — A Hypothesis date = 2020-09-24 pages = extension = .txt mime = text/plain words = 2465 sentences = 108 flesch = 38 summary = While long-term exposure to air pollutants such as PM 2.5 and nitrous dioxide contributes to persistent inflammatory responses and cardiopulmonary diseases (7) , which might increase vulnerability to COVID-19, it is also plausible that depending on the environment SARS-CoV-2 "hitchhiking" on airborne PM pollutants might be an additional mechanism for spreading the infection. In summary, although long-term exposure to polluted air might increase vulnerability to COVID-19 through prior adverse cellular effects of settled PM (24), our proposed "hitchhiking" hypothesis offers an additional multi-mechanistic pathogenic process through delivery of low viral titres with diverse PM-virus composites and is applicable to both indoor and outdoor situations, where the pathogenic severity is dependent on PM concentration, composition, shape and size as well as the infectious viral load. Contrary to the suggestions that long-term exposure to PM might increase vulnerability to SAR-CoV-2 infection, inhaled PM might promote some forms of immunity to the virus in some individuals. cache = ./cache/cord-354353-hyz0gmpz.txt txt = ./txt/cord-354353-hyz0gmpz.txt === reduce.pl bib === id = cord-350041-b1vmnwv2 author = Cena, Hellas title = Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection? date = 2020-05-07 pages = extension = .txt mime = text/plain words = 3017 sentences = 147 flesch = 35 summary = There has been a gradual increase in studies exploring prevention and control measures, and we recommend paying close attention to nutrition, which may contribute to modulating some important consequences of COVID-19 infection, as such pro-inflammatory cytokine storm. Unfortunately, we do not yet have weight, height, and waist circumference data for all patients with laboratory-confirmed COVID-19, and, therefore, we cannot disentangle the effects of adiposity on lung function and immune response to viral infection. Recent data on patients with laboratory-confirmed COVID-19 treated at an academic health institution in New York City, the epicenter of the COVID-19 outbreak in the United States, between March 1, 2020, and April 2, 2020, with follow up through April 7, 2020 (13, 14) showed that obesity, after age, was linked to more severe coronavirus cases, with a substantially higher odds ratio than any cardiovascular or pulmonary disease. cache = ./cache/cord-350041-b1vmnwv2.txt txt = ./txt/cord-350041-b1vmnwv2.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-336201-fl606l3b author = Daryabor, Gholamreza title = The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System date = 2020-07-22 pages = extension = .txt mime = text/plain words = 13863 sentences = 715 flesch = 38 summary = Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. T2DM, the most common form of diabetes (∼90%), is characterized by a systemic inflammatory disease accompanied by insulin resistance (IR) or decreased metabolic response to insulin in several tissues, including the adipose tissue, liver, and skeletal muscle, as well as by reduced insulin synthesis by pancreatic beta cells (4, 5) . During the progression of diabetes, hyperglycemia promotes mitochondrial dysfunction and induces the formation of reactive oxygen species (ROS) that cause oxidative stress in several tissues such as blood vessels and pancreatic beta cells (7) (8) (9) . In addition, the attachment of AGEs to their receptors [e.g., CD36, galectin-3, scavenger receptors types I (SR-A1), and II (SR-A2)] on the surfaces of immune cells in the circulation and tissues activates the expression of pro-inflammatory cytokines and increases free radical generation (18) . cache = ./cache/cord-336201-fl606l3b.txt txt = ./txt/cord-336201-fl606l3b.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-352737-3ttrx3lf author = Cunha, Lucas Leite title = Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response date = 2020-08-07 pages = extension = .txt mime = text/plain words = 6824 sentences = 337 flesch = 37 summary = Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Interestingly, polymorphonuclear leucocytes from the elderly are less capable of modulating the triggering receptor expressed on myeloid cell-1 (TREM-1)-induced oxidative bursts, suggesting that TREM-1 signal transduction altered with aging may be one of the mediators of the decrease in microbicidal potential of innate immune cells in older adults (41) . cache = ./cache/cord-352737-3ttrx3lf.txt txt = ./txt/cord-352737-3ttrx3lf.txt === reduce.pl bib === id = cord-354030-8tfg881h author = Dong, Rong title = Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date = 2020-07-28 pages = extension = .txt mime = text/plain words = 7983 sentences = 442 flesch = 52 summary = The realm of immunoinformatics tools considers the mechanism of the host immune response to yield additional methodologies in the design of vaccine against diseases are cost-effective and convenient, as in silico predictions can reduce the number of experiments needed (13, 14) . In this present, we employed immunoinformatics to predict multiple immunogenic proteins from the SARS-CoV-2 proteome and thereby design a multi-epitope vaccine. developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . A vaccine based on the spike protein could induce antibodies to block SARS-COV-2 binding and fusion or neutralize virus infection (18) , as well as induce harmful immune responses that cause liver damage (19) . To design an effective vaccine, we selected the SARS-CoV-2 protein through the above-mentioned methods for epitope prediction. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach cache = ./cache/cord-354030-8tfg881h.txt txt = ./txt/cord-354030-8tfg881h.txt === reduce.pl bib === id = cord-339152-wfakzb6w author = Trovato, Maria title = Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date = 2020-09-03 pages = extension = .txt mime = text/plain words = 12000 sentences = 540 flesch = 38 summary = Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential. cache = ./cache/cord-339152-wfakzb6w.txt txt = ./txt/cord-339152-wfakzb6w.txt === reduce.pl bib === ===== Reducing email addresses cord-003545-corvd5cs Creating transaction Updating adr table ===== Reducing keywords cord-003091-uvfppirt cord-257662-viy65y72 cord-253108-p3wlw5d4 cord-263141-n200x6z1 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cord-283382-t890r7xp cord-297960-4x1j0iqg cord-300429-b0zev8zb cord-304623-j9ay4jkf cord-286337-qk90xb3a cord-318418-uqxzds6g cord-332150-j76726no cord-348283-7xorq5ce cord-333932-aqcllik0 cord-336924-7xcbtn3q cord-321401-w4ne60fn cord-295302-vwrxentv cord-282336-zvc04s39 cord-255578-0ltb9dpa cord-020770-wpub7krf cord-268511-dx2cqqt5 cord-319729-6lzjhn8j cord-328003-yovp8squ cord-340475-h0q1m3ed cord-330417-8nnobx8g cord-334564-bqh9jkds cord-352230-8mazd3eu cord-320474-jyk7zphp cord-353887-f4yd7guj cord-306600-cxz8hf9q cord-316702-dj2fo8sn cord-353594-z1vxamvp cord-336201-fl606l3b cord-354030-8tfg881h cord-284867-p4jgyusp cord-003656-7mzsaz7a cord-277529-z2r14w2k cord-263433-oldy0gta cord-259131-36udb7uc cord-261367-i1n8x0uc cord-350041-b1vmnwv2 cord-317797-h229skaq cord-282081-qaagup4d cord-341513-e6p3lrlf cord-351431-xcqz9d3t Creating transaction Updating url table ===== Reducing named entities cord-033488-du8heorx cord-003378-0ozhye9q cord-004151-9815ikzg cord-003545-corvd5cs 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cord-312955-gs65c3fy cord-312075-asbt0mcj cord-336924-7xcbtn3q cord-354353-hyz0gmpz cord-352960-pfccsgco cord-332150-j76726no cord-323590-m4jsu1q5 cord-350836-1enteev7 cord-333041-69n2wwn3 cord-320474-jyk7zphp cord-328763-hcbs20a0 cord-354030-8tfg881h cord-352150-ey9kc7zj cord-351431-xcqz9d3t cord-343824-00mqmpzw cord-336201-fl606l3b cord-352737-3ttrx3lf cord-354620-xf6glr2h cord-352230-8mazd3eu cord-339152-wfakzb6w cord-353887-f4yd7guj cord-267237-wbwlfx7q Creating transaction Updating ent table ===== Reducing parts of speech cord-003378-0ozhye9q cord-033488-du8heorx cord-004151-9815ikzg cord-003656-7mzsaz7a cord-267567-w39f584z cord-030803-6i0e2zkd cord-265005-e6rpryrh cord-268781-6l74rrlm cord-265855-zf52vl11 cord-003545-corvd5cs cord-268501-z4oztgi0 cord-259748-x7dq1sy4 cord-003091-uvfppirt cord-003122-a3f4l6iu cord-261367-i1n8x0uc cord-001674-tp4o7fxx cord-034310-izpt032p cord-267134-5gz2dotn cord-284867-p4jgyusp cord-268438-bjs5oliw cord-257662-viy65y72 cord-003319-u88gznxq cord-263141-n200x6z1 cord-015254-xtox2rxs cord-253108-p3wlw5d4 cord-000647-uofygmeu cord-003368-f8f2utzx cord-003825-tkqxb1ql cord-262575-06i2nv0t cord-282336-zvc04s39 cord-284156-btb4oodz cord-032953-qy4b2l2f cord-257116-6td3efjw cord-262673-j2ot35lt cord-255578-0ltb9dpa cord-262944-9k64f0tw cord-262375-1ex2ow07 cord-259131-36udb7uc cord-030385-btf502ju cord-267237-wbwlfx7q cord-020770-wpub7krf cord-279105-e2zjxjox cord-288496-7rrh2gg6 cord-004477-qu2o2iu1 cord-280924-g6062fwk cord-252568-b8sbvy0g cord-003685-jcvrqeew cord-297790-tpjxt0w5 cord-268483-joiajgs4 cord-003724-705h5l06 cord-254809-o454k6ae cord-254192-86ksgl5t cord-298458-p7rvupjo cord-003914-ss8vdpox cord-298604-tn8hc6jv cord-269170-9f460xbq cord-256998-or73in8m cord-255034-x100xo2t cord-260452-js4nr4d8 cord-280605-2i4gk7et cord-274557-2071770h cord-278081-tk7vn1v1 cord-283505-ousbar6c cord-003598-m2fsrwvw cord-268511-dx2cqqt5 cord-026866-0hlre9i6 cord-256582-x2grfhov cord-267166-ecmayzr6 cord-277529-z2r14w2k cord-003828-bhfghcby cord-278839-uu2wlpmp cord-291941-9a4tt4f7 cord-253862-jl1zhg13 cord-280941-ds6x0yym cord-266085-914y3je0 cord-263433-oldy0gta cord-269222-g2ibmo75 cord-264814-v4wnmg03 cord-273505-pcsw3vmx cord-275779-ocbygkyb cord-293736-nyvwv31m cord-283382-t890r7xp cord-285760-y37ji92k cord-295416-y3lvcjqd cord-303017-4zx94rm6 cord-282081-qaagup4d cord-300429-b0zev8zb cord-297960-4x1j0iqg cord-296585-yfh5d4io cord-286337-qk90xb3a cord-273277-4ewvwg4o cord-304626-ffao7vka cord-284409-xiyeceib cord-304619-tpv76833 cord-306600-cxz8hf9q cord-295302-vwrxentv cord-302295-nblmshni cord-271419-v6dfel3l cord-272491-a84pahdr cord-305936-tdswzj7r cord-312074-0nqmjdek cord-308433-vrkdtrfz cord-307813-elom30nx cord-313227-6zwkfzab cord-304623-j9ay4jkf cord-313117-0qur0isb cord-312438-zr9zx7pv cord-312955-gs65c3fy cord-319774-mkz7z38o cord-319729-6lzjhn8j cord-318418-uqxzds6g cord-321401-w4ne60fn cord-317797-h229skaq cord-312075-asbt0mcj cord-320431-0877trhh cord-333670-qv1orlv5 cord-313431-swkcdvx8 cord-333932-aqcllik0 cord-332150-j76726no cord-323756-atnrw9ew cord-328011-6lf3no6u cord-340228-mvqoyror cord-318630-h6j7iqbm cord-328549-r56lih8j cord-338261-tyimwctm cord-348283-7xorq5ce cord-344610-mqq6fmsp cord-340475-h0q1m3ed cord-344829-adlp2rjy cord-338498-3238fz73 cord-321568-okvt1fg3 cord-341513-e6p3lrlf cord-333041-69n2wwn3 cord-325129-faptufak cord-330417-8nnobx8g cord-342776-hkjhqgie cord-320663-xypg6evo cord-316702-dj2fo8sn cord-350492-1s6wtj25 cord-328003-yovp8squ cord-353217-gmc3qrci cord-353594-z1vxamvp cord-325353-tx6s4ggu cord-320474-jyk7zphp cord-344093-3bniy5b5 cord-351305-6vtv2xuh cord-334564-bqh9jkds cord-323590-m4jsu1q5 cord-336924-7xcbtn3q cord-350041-b1vmnwv2 cord-340741-bhxm4zua cord-352960-pfccsgco cord-338092-barmkkwx cord-351431-xcqz9d3t cord-354353-hyz0gmpz cord-346389-gbmnoo84 cord-353887-f4yd7guj cord-336201-fl606l3b cord-328763-hcbs20a0 cord-350836-1enteev7 cord-352230-8mazd3eu cord-352150-ey9kc7zj cord-354620-xf6glr2h cord-354030-8tfg881h cord-352737-3ttrx3lf cord-343824-00mqmpzw cord-339152-wfakzb6w Creating transaction Updating pos table Building ./etc/reader.txt cord-256998-or73in8m cord-338092-barmkkwx cord-318630-h6j7iqbm cord-265005-e6rpryrh cord-259748-x7dq1sy4 cord-350836-1enteev7 number of items: 167 sum of words: 815,831 average size in words: 6,687 average readability score: 43 nouns: cells; cell; infection; virus; patients; response; expression; protein; mice; disease; responses; activation; vaccine; role; influenza; type; lung; receptor; levels; study; production; studies; infections; immunity; macrophages; antibody; proteins; host; antibodies; coronavirus; activity; inflammation; viruses; treatment; rig; syndrome; antigen; cytokines; data; analysis; effects; cytokine; development; vaccines; gene; genes; system; function; factor; pathway verbs: induced; shown; used; increase; associated; mediated; including; binding; activated; signaling; infected; found; expressed; following; reducing; compared; led; suggest; based; inhibits; demonstrated; promotes; caused; identified; regulate; observed; targeting; reported; produced; resulting; enhancing; involved; provided; requires; contributed; related; developing; described; derived; indicated; treated; decreased; performed; plays; stimulated; containing; revealed; controlling; prevent; generated adjectives: immune; viral; human; respiratory; inflammatory; specific; severe; anti; innate; clinical; acute; high; different; antiviral; non; several; epithelial; chronic; like; important; potential; dependent; novel; bacterial; pulmonary; higher; cellular; multiple; dendritic; covid-19; significant; low; early; similar; regulatory; single; pro; new; lower; major; many; healthy; functional; molecular; therapeutic; recent; primary; protective; first; positive adverbs: also; however; well; significantly; therefore; highly; recently; furthermore; previously; even; respectively; interestingly; moreover; still; directly; together; indeed; currently; potentially; similarly; mainly; finally; particularly; especially; additionally; yet; less; specifically; rapidly; first; subsequently; often; thereby; prior; rather; importantly; strongly; likely; already; alone; hence; primarily; later; long; now; relatively; negatively; fully; differentially; far pronouns: it; we; i; their; its; they; our; them; us; itself; his; one; my; themselves; he; iga1; her; you; mov18; iga2; ifitm3; mrnas; your; pdcs; isgf3; ifnar1; stat1; she; me; il-1β; zbtrim25; stnfα; rhil-10; ours; ns3/4a; ilc1s; il-1-and; igg1; ≥10×; λr1; α2-macroglobulin; u; tnf)-α; tj003234; t(h)17; srebp2; siga1; samples:"you; rig-; rad5 proper nouns: SARS; T; IFN; CoV-2; CD8; COVID-19; RNA; CD4; NK; CoV; IL-12; C; IL-6; TNF; HLA; I; IAV; IL-10; RSV; MERS; MHC; S; α; II; COPD; B; China; LPS; MS; γ; CSF; HIV-1; Figure; HIV; ACE2; IgA; IgG; GM; |; USA; DCs; A; MDA5; PBS; β; CNS; MAVS; ARDS; Supplementary; TTP keywords: sars; cell; covid-19; ifn; cd8; rna; virus; infection; patient; cov-2; cd4; vaccine; rig; il-6; mers; dna; type; tnf; lps; iav; respiratory; protein; influenza; hla; antibody; ace2; viral; severe; rsv; response; pbs; mhc; irf3; immune; hcv; epitope; disease; copd; cns; ards; zika; vaccination; trim25; tlr4; th1; tbk1; sepsis; rbd; prrsv; pedv one topic; one dimension: cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030256/ titles(s): Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines three topics; one dimension: sars; cells; cell file(s): https://doi.org/10.3389/fimmu.2019.01586, https://doi.org/10.3389/fimmu.2020.01698, https://www.ncbi.nlm.nih.gov/pubmed/32983097/ titles(s): Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5 | Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung | A Systematic, Unbiased Mapping of CD8(+) and CD4(+) T Cell Epitopes in Yellow Fever Vaccinees five topics; three dimensions: cells il infection; virus sars cov; patients covid cells; cells il cell; cell cells antibodies file(s): https://doi.org/10.3389/fimmu.2018.01249, https://doi.org/10.3389/fimmu.2019.01586, https://doi.org/10.3389/fimmu.2020.01170, https://www.ncbi.nlm.nih.gov/pubmed/33178203/, https://www.ncbi.nlm.nih.gov/pubmed/32983097/ titles(s): Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma | Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5 | Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health | Localized Interleukin-12 for Cancer Immunotherapy | A Systematic, Unbiased Mapping of CD8(+) and CD4(+) T Cell Epitopes in Yellow Fever Vaccinees Type: cord title: journal-frontImmunol-cord date: 2021-05-30 time: 15:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"Front Immunol" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-271419-v6dfel3l author: Adachi, Shun title: Commentary: Origin and evolution of pathogenic coronaviruses date: 2020-04-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32373134/ doi: 10.3389/fimmu.2020.00811 id: cord-262673-j2ot35lt author: Ahmed-Hassan, Hanaa title: Innate Immune Responses to Highly Pathogenic Coronaviruses and Other Significant Respiratory Viral Infections date: 2020-08-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The new pandemic virus SARS-CoV-2 emerged in China and spread around the world in <3 months, infecting millions of people, and causing countries to shut down public life and businesses. Nearly all nations were unprepared for this pandemic with healthcare systems stretched to their limits due to the lack of an effective vaccine and treatment. Infection with SARS-CoV-2 can lead to Coronavirus disease 2019 (COVID-19). COVID-19 is respiratory disease that can result in a cytokine storm with stark differences in morbidity and mortality between younger and older patient populations. Details regarding mechanisms of viral entry via the respiratory system and immune system correlates of protection or pathogenesis have not been fully elucidated. Here, we provide an overview of the innate immune responses in the lung to the coronaviruses MERS-CoV, SARS-CoV, and SARS-CoV-2. This review provides insight into key innate immune mechanisms that will aid in the development of therapeutics and preventive vaccines for SARS-CoV-2 infection. url: https://doi.org/10.3389/fimmu.2020.01979 doi: 10.3389/fimmu.2020.01979 id: cord-340228-mvqoyror author: Al-Herz, Waleed title: Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry date: 2019-05-29 words: 2930.0 sentences: 170.0 pages: flesch: 42.0 cache: ./cache/cord-340228-mvqoyror.txt txt: ./txt/cord-340228-mvqoyror.txt summary: Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The distribution of these patients according to PID categories is: immunodeficiencies affecting cellular and humoral immunity, 97 patients (35.4%); combined immunodeficiencies with associated syndromic features, 67 patients (24.5%); predominantly antibody deficiencies, 34 patients (12.4%); diseases of immune dysregulation, 47 patients (17.2%); congenital defects of phagocyte number or function, 17 patients (6.2%); autoinflammatory disorders, 1 patient (0.3%); and complement deficiencies, 11 patients (4%). abstract: Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality. url: https://www.ncbi.nlm.nih.gov/pubmed/31191561/ doi: 10.3389/fimmu.2019.01231 id: cord-278839-uu2wlpmp author: Alberca, Ricardo Wesley title: Pregnancy, Viral Infection, and COVID-19 date: 2020-07-07 words: 7237.0 sentences: 368.0 pages: flesch: 43.0 cache: ./cache/cord-278839-uu2wlpmp.txt txt: ./txt/cord-278839-uu2wlpmp.txt summary: In 2009, during the H1N1 flu pandemic, an increased ratio of female to male cases was verified, in which pregnant women developed more complications, as severe acute respiratory syndrome, and higher mortality compared to the general population (30, 31) . Additionally, infection by the Lassa virus in pregnant women shows high levels of placental replication, and the risk of maternal-fetal mortality increases with the duration of pregnancy (38, 39) . At first, contagion occurred through contact with some infected animals but, soon there were the first reports of human-to-human transmission (93), The virus was identified as belonging to the coronaviridae family and was designated SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) (94). Chen and collaborators, verified alteration in calcium and albumin levels in the blood of pregnant women with SARS-CoV-2 infection (124) , which could potentially increase the severity in COVID-19 (125) . abstract: Pregnancy comprises a unique immunological condition, to allow fetal development and to protect the host from pathogenic infections. Viral infections during pregnancy can disrupt immunological tolerance and may generate deleterious effects on the fetus. Despite these possible links between pregnancy and infection-induced morbidity, it is unclear how pregnancy interferes with maternal response to some viral pathogens. In this context, the novel coronavirus (SARS-CoV-2) can induce the coronavirus diseases-2019 (COVID-19) in pregnant women. The potential risk of vertical transmission is unclear, babies born from COVID-19-positive mothers seems to have no serious clinical symptoms, the possible mechanisms are discussed, which highlights that checking the children's outcome and more research is warranted. In this review, we investigate the reports concerning viral infections and COVID-19 during pregnancy, to establish a correlation and possible implications of COVID-19 during pregnancy and neonatal's health. url: https://www.ncbi.nlm.nih.gov/pubmed/32733490/ doi: 10.3389/fimmu.2020.01672 id: cord-321568-okvt1fg3 author: Alberca, Ricardo Wesley title: Perspective: The Potential Effects of Naringenin in COVID-19 date: 2020-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), was declared a pandemic by the World Health Organization in March 2020. Severe COVID-19 cases develop severe acute respiratory syndrome, which can result in multiple organ failure, sepsis, and death. The higher risk group includes the elderly and subjects with pre-existing chronic illnesses such as obesity, hypertension, and diabetes. To date, no specific treatment or vaccine is available for COVID-19. Among many compounds, naringenin (NAR) a flavonoid present in citrus fruits has been investigated for antiviral and anti-inflammatory properties like reducing viral replication and cytokine production. In this perspective, we summarize NAR potential anti-inflammatory role in COVID-19 associated risk factors and SARS-CoV-2 infection. url: https://www.ncbi.nlm.nih.gov/pubmed/33101291/ doi: 10.3389/fimmu.2020.570919 id: cord-280605-2i4gk7et author: Bachmann, María Consuelo title: The Challenge by Multiple Environmental and Biological Factors Induce Inflammation in Aging: Their Role in the Promotion of Chronic Disease date: 2020-10-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The aging process is driven by multiple mechanisms that lead to changes in energy production, oxidative stress, homeostatic dysregulation and eventually to loss of functionality and increased disease susceptibility. Most aged individuals develop chronic low-grade inflammation, which is an important risk factor for morbidity, physical and cognitive impairment, frailty, and death. At any age, chronic inflammatory diseases are major causes of morbimortality, affecting up to 5–8% of the population of industrialized countries. Several environmental factors can play an important role for modifying the inflammatory state. Genetics accounts for only a small fraction of chronic-inflammatory diseases, whereas environmental factors appear to participate, either with a causative or a promotional role in 50% to 75% of patients. Several of those changes depend on epigenetic changes that will further modify the individual response to additional stimuli. The interaction between inflammation and the environment offers important insights on aging and health. These conditions, often depending on the individual’s sex, appear to lead to decreased longevity and physical and cognitive decline. In addition to biological factors, the environment is also involved in the generation of psychological and social context leading to stress. Poor psychological environments and other sources of stress also result in increased inflammation. However, the mechanisms underlying the role of environmental and psychosocial factors and nutrition on the regulation of inflammation, and how the response elicited for those factors interact among them, are poorly understood. Whereas certain deleterious environmental factors result in the generation of oxidative stress driven by an increased production of reactive oxygen and nitrogen species, endoplasmic reticulum stress, and inflammation, other factors, including nutrition (polyunsaturated fatty acids) and behavioral factors (exercise) confer protection against inflammation, oxidative and endoplasmic reticulum stress, and thus ameliorate their deleterious effect. Here, we discuss processes and mechanisms of inflammation associated with environmental factors and behavior, their links to sex and gender, and their overall impact on aging. url: https://www.ncbi.nlm.nih.gov/pubmed/33162985/ doi: 10.3389/fimmu.2020.570083 id: cord-291941-9a4tt4f7 author: Barber-Axthelm, Isaac M. title: Understanding the Role of Mucosal-Associated Invariant T-Cells in Non-human Primate Models of HIV Infection date: 2020-08-18 words: 5258.0 sentences: 252.0 pages: flesch: 43.0 cache: ./cache/cord-291941-9a4tt4f7.txt txt: ./txt/cord-291941-9a4tt4f7.txt summary: Herein, we discuss the current state of MAIT cell characterization in NHPs [which has focused on rhesus macaques (RM), pigtail macaques (PTM), and Mauritian cynomolgus macaques (MCM)] and the changes in MAIT cell populations that occur during simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infection, which are the critical animal models for HIV infection. MAIT cells are consistently maintained at low frequencies in secondary lymphoid organs (lymph nodes and spleen) compared to the peripheral blood, in both humans and NHPs. This is attributed to the relative lack of CCR7 and CD62L expression, both required for lymphoid tissue homing, on peripheral MAIT cells [reviewed in Kurioka et al. The lack of MAIT cell depletion during acute infection is consistent with what has been observed in humans during initial HIV infection and emphasizes the importance of the NHP-SIV/SHIV model to study MAIT cell dynamics during peracute infection. abstract: Chronic HIV infection causes systemic immune activation and dysregulation, resulting in the impairment of most T-cell subsets including MAIT cells. Multiple human cohort studies demonstrate MAIT cells are selectively depleted in the peripheral blood and lymphoid tissues during HIV infection, with incomplete restoration during suppressive antiretroviral therapy. Because MAIT cells play an important role in mucosal defense against a wide array of pathogens, fully reconstituting the MAIT cell compartment in ART-treated populations could improve immunity against co-infections. Non-human primates (NHPs) are a valuable, well-described animal model for HIV infection in humans. NHPs also maintain MAIT cell frequencies more comparable to humans, compared to other common animal models, and provide a unique opportunity to study MAIT cells in the circulation and mucosal tissues in a longitudinal manner. Only recently, however, have NHP MAIT cells been thoroughly characterized using macaque-specific MR1 tetramer reagents. Here we review the similarities and differences between MAIT cells in humans and NHPs as well as the impact of SIV/SHIV infection on MAIT cells and the potential implications for future research. url: https://www.ncbi.nlm.nih.gov/pubmed/33013862/ doi: 10.3389/fimmu.2020.02038 id: cord-303017-4zx94rm6 author: Barbieri, Antonio title: Can Beta-2-Adrenergic Pathway Be a New Target to Combat SARS-CoV-2 Hyperinflammatory Syndrome?—Lessons Learned From Cancer date: 2020-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: SARS-CoV-2 infection is a new threat to global public health in the 21(st) century (2020), which has now rapidly spread around the globe causing severe pneumonia often linked to Acute Respiratory Distress Syndrome (ARDS) and hyperinflammatory syndrome. SARS-CoV-2 is highly contagious through saliva droplets. The structural analysis suggests that the virus enters human cells through the ligation of the spike protein to angiotensin-converting enzyme 2 (ACE(2)). The progression of Covid-19 has been divided into three main stages: stage I—viral response, stage II—pulmonary phase, and stage III—hyperinflammation phase. Once the patients enter stage III, it will likely need ventilation and it becomes difficult to manage. Thus, it will be of paramount importance to find therapies to prevent or slow down the progression of the disease toward stage III. The key event leading to hyperinflammation seems to be the activation of Th-17 immunity response and Cytokine storm. B(2)-adrenergic receptors (B(2)ARs) are expressed on airways and on all the immune cells such as macrophages, dendritic cells, B and T lymphocytes. Blocking (B(2)AR) has been proven, also in clinical settings, to reduce Th-17 response and negatively modulate inflammatory cytokines including IL-6 while increasing IFNγ. Non-selective beta-blockers are currently used to treat several diseases and have been proven to reduce stress-induced inflammation and reduce anxiety. For these reasons, we speculate that targeting B(2)AR in the early phase of Covid-19 might be beneficial to prevent hyperinflammation. url: https://doi.org/10.3389/fimmu.2020.588724 doi: 10.3389/fimmu.2020.588724 id: cord-263433-oldy0gta author: Barriocanal, Marina title: Long Non-Coding RNA BST2/BISPR is Induced by IFN and Regulates the Expression of the Antiviral Factor Tetherin date: 2015-01-09 words: 8773.0 sentences: 497.0 pages: flesch: 50.0 cache: ./cache/cord-263433-oldy0gta.txt txt: ./txt/cord-263433-oldy0gta.txt summary: As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. To address the issue of whether IFN could also regulate expression of lncRNAs, which may play key roles in the antiviral response, we analyzed the transcriptome of cells treated or not with IFNα2 by RNA sequencing (RNASeq). The results showed that at later times post-infection with the influenza virus lacking NS1, there was increased expression of lncISG15, lncBST2/BISPR, and their neighboring coding transcripts (Figure 3A) . To discriminate whether lncISG15 and lncBST2/BISPR are induced directly by the JAK/STAT signaling pathway or by a secondary wave of the IFN response, we evaluated the expression of these lncRNAs and their coding neighboring genes in HuH7 or A549 cells incubated or not with the JAK/STAT inhibitor ruxolitinib. abstract: Many long non-coding RNAs (lncRNAs) are expressed in cells but only a few have been well characterized. In these cases, lncRNAs have been shown to be key regulators of several cellular processes. Therefore, there is a great need to understand the function of more lncRNAs and their regulation in response to stimuli. Interferon (IFN) is a key molecule in the cellular antiviral response. IFN binding to its receptor activates transcription of several IFN-stimulated genes (ISGs) that function as potent antivirals. In addition, several ISGs are positive or negative regulators of the IFN pathway. This is essential to ensure a strong antiviral response and a later return of the cell to homeostasis. As the ISGs described to date are coding genes, we sought to determine whether IFN also regulates the expression of long non-coding ISGs. To this aim, we used RNA sequencing to analyze the transcriptome of control and HuH7 cells treated with IFNα2. The results show that IFN-treatment regulates the expression of several unknown non-coding transcripts. We have validated two lncRNAs upregulated after treatment with different doses of type I IFNα2 in different cells or with type III IFNλ. These lncRNAs were also induced by influenza and vesicular stomatitis virus mutants unable to block the IFN response, but not by several wild-type lytic viruses tested. These lncRNA genes were named lncISG15 and lncBST2 as they are located close to ISGs ISG15 and BST2, respectively. Interestingly, inhibition experiments showed that lncBST2 is a positive regulator of BST2. Therefore lncBST2 has been renamed BISPR, from BST2 IFN-stimulated positive regulator. Our results may have therapeutic implications as lncBST2/BISPR, but also lncISG15 and their coding neighbors, are increased in cells infected with hepatitis C virus and in the liver of infected patients. These results allow us to hypothesize that several lncRNAs could be activated by IFN to control the potency of the antiviral IFN response. url: https://www.ncbi.nlm.nih.gov/pubmed/25620967/ doi: 10.3389/fimmu.2014.00655 id: cord-313431-swkcdvx8 author: Becerra-Diaz, Mireya title: Androgen and Androgen Receptors as Regulators of Monocyte and Macrophage Biology in the Healthy and Diseased Lung date: 2020-08-07 words: 14972.0 sentences: 789.0 pages: flesch: 40.0 cache: ./cache/cord-313431-swkcdvx8.txt txt: ./txt/cord-313431-swkcdvx8.txt summary: The opposite effects seen in different inflammatory contexts highlight the need for a deeper and broader study of the androgen/ARmediated modulation of monocytes and macrophages, as these cells participate in both the initial and late phases of immune responses in a variety of diseases. Studies of androgen receptor function in human monocytes and macrophages have focused primarily on the roles of male sex and sex hormones in promoting atherosclerotic foam cell formation (196) and inhibiting cutaneous wound healing (186, 215) . There is a paucity of literature regarding how introducing or depleting exogenous sex hormones (such as in female-to-male transgender individuals receiving testosterone supplementation or women with estrogen blockade) affects the function of blood monocytes and lung macrophages in men and women with asthma. Modulation of monocyte and macrophage function mediated by the interaction of androgen and AR has been examined mostly by correlative studies in humans following lifespan changes in sex hormones or using hormonal manipulation in mouse models of lung disease. abstract: Androgens, the predominant male sex hormones, drive the development and maintenance of male characteristics by binding to androgen receptor (AR). As androgens are systemically distributed throughout the whole organism, they affect many tissues and cell types in addition to those in male sexual organs. It is now clear that the immune system is a target of androgen action. In the lungs, many immune cells express ARs and are responsive to androgens. In this review, we describe the effects of androgens and ARs on lung myeloid immune cells—monocytes and macrophages—as they relate to health and disease. In particular, we highlight the effect of androgens on lung diseases, such as asthma, chronic obstructive pulmonary disease and lung fibrosis. We also discuss the therapeutic use of androgens and how circulating androgens correlate with lung disease. In addition to human studies, we also discuss how mouse models have helped to uncover the effect of androgens on monocytes and macrophages in lung disease. Although the role of estrogen and other female hormones has been broadly analyzed in the literature, we focus on the new perspectives of androgens as modulators of the immune system that target myeloid cells during lung inflammation. url: https://doi.org/10.3389/fimmu.2020.01698 doi: 10.3389/fimmu.2020.01698 id: cord-352230-8mazd3eu author: Beeraka, Narasimha M. title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. url: https://doi.org/10.3389/fimmu.2020.552925 doi: 10.3389/fimmu.2020.552925 id: cord-020770-wpub7krf author: Benmamar-Badel, Anouk title: Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies date: 2020-04-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these “microglial signatures” have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7147523/ doi: 10.3389/fimmu.2020.00430 id: cord-320474-jyk7zphp author: Bonaventura, Aldo title: Targeting GM-CSF in COVID-19 Pneumonia: Rationale and Strategies date: 2020-07-03 words: 5082.0 sentences: 242.0 pages: flesch: 38.0 cache: ./cache/cord-320474-jyk7zphp.txt txt: ./txt/cord-320474-jyk7zphp.txt summary: Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Data supporting the role of hyperinflammation in sepsisrelated acute respiratory distress syndrome (ARDS) are derived from a sub-group analysis of a phase 3 randomized controlled trial of IL-1 receptor antagonist (anakinra), which showed significant survival benefit in patients treated with anakinra compared to placebo (15) . APC, antigen presenting cell; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. A randomized, double-blind, placebo-controlled phase II study tested the effects of low-dose hrGM-CSF (molgramostim, 3 µg/kg daily) for 5 days in patients in addition to the standard of care in critically ill patients with severe sepsis and respiratory dysfunction (65) . abstract: COVID-19 is a clinical syndrome ranging from mild symptoms to severe pneumonia that often leads to respiratory failure, need for mechanical ventilation, and death. Most of the lung damage is driven by a surge in inflammatory cytokines [interleukin-6, interferon-γ, and granulocyte-monocyte stimulating factor (GM-CSF)]. Blunting this hyperinflammation with immunomodulation may lead to clinical improvement. GM-CSF is produced by many cells, including macrophages and T-cells. GM-CSF-derived signals are involved in differentiation of macrophages, including alveolar macrophages (AMs). In animal models of respiratory infections, the intranasal administration of GM-CSF increased the proliferation of AMs and improved outcomes. Increased levels of GM-CSF have been recently described in patients with COVID-19 compared to healthy controls. While GM-CSF might be beneficial in some circumstances as an appropriate response, in this case the inflammatory response is maladaptive by virtue of being later and disproportionate. The inhibition of GM-CSF signaling may be beneficial in improving the hyperinflammation-related lung damage in the most severe cases of COVID-19. This blockade can be achieved through antagonism of the GM-CSF receptor or the direct binding of circulating GM-CSF. Initial findings from patients with COVID-19 treated with a single intravenous dose of mavrilimumab, a monoclonal antibody binding GM-CSF receptor α, showed oxygenation improvement and shorter hospitalization. Prospective, randomized, placebo-controlled trials are ongoing. Anti-GM-CSF monoclonal antibodies, TJ003234 and gimsilumab, will be tested in clinical trials in patients with COVID-19, while lenzilumab received FDA approval for compassionate use. These trials will help inform whether blunting the inflammatory signaling provided by the GM-CSF axis in COVID-19 is beneficial. url: https://www.ncbi.nlm.nih.gov/pubmed/32719685/ doi: 10.3389/fimmu.2020.01625 id: cord-336924-7xcbtn3q author: Borghi, Maria Orietta title: Anti-Phospholipid Antibodies in COVID-19 Are Different From Those Detectable in the Anti-Phospholipid Syndrome date: 2020-10-15 words: 3190.0 sentences: 185.0 pages: flesch: 48.0 cache: ./cache/cord-336924-7xcbtn3q.txt txt: ./txt/cord-336924-7xcbtn3q.txt summary: OBJECTIVE: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β(2)GPI antibodies. aPL in COVID-19 patients are mainly directed against β(2)GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome. The prevalence of COVID-19 patients positive for aCL and anti-b 2 GPI IgG/IgA/ IgM detected by ELISA and CIA is summarized in Table 2 . Again, there was no association between prolonged aPTT and the presence of aPS/PT antibodies nor with thrombotic events in our COVID-19 cohort. Again, there was no association between prolonged aPTT and the presence of aPS/PT antibodies nor with thrombotic events in our COVID-19 cohort. In conclusion, while the medium/high aPL titers with D1 specificity are associated with vascular events in APS, low antibody titers with reactivity against b 2 GPI epitope(s) different from D1 or D4,5 can be found in COVID-19. abstract: BACKGROUND: Critically ill patients with coronavirus disease 2019 (COVID-19) have a profound hypercoagulable state and often develop coagulopathy which leads to organ failure and death. Because of a prolonged activated partial-thromboplastin time (aPTT), a relationship with anti-phospholipid antibodies (aPLs) has been proposed, but results are controversial. Functional assays for aPL (i.e., lupus anticoagulant) can be influenced by concomitant anticoagulation and/or high levels of C reactive protein. The presence of anti-cardiolipin (aCL), anti-beta2-glycoprotein I (anti-β(2)GPI), and anti-phosphatidylserine/prothrombin (aPS/PT) antibodies was not investigated systematically. Epitope specificity of anti-β(2)GPI antibodies was not reported. OBJECTIVE: To evaluate the prevalence and the clinical association of aPL in a large cohort of COVID-19 patients, and to characterize the epitope specificity of anti-β(2)GPI antibodies. METHODS: ELISA and chemiluminescence assays were used to test 122 sera of patients suffering from severe COVID-19. Of them, 16 displayed major thrombotic events. RESULTS: Anti-β(2)GPI IgG/IgA/IgM was the most frequent in 15.6/6.6/9.0% of patients, while aCL IgG/IgM was detected in 5.7/6.6% by ELISA. Comparable values were found by chemiluminescence. aPS/PT IgG/IgM were detectable in 2.5 and 9.8% by ELISA. No association between thrombosis and aPL was found. Reactivity against domain 1 and 4-5 of β(2)GPI was limited to 3/58 (5.2%) tested sera for each domain and did not correlate with aCL/anti-β(2)GPI nor with thrombosis. CONCLUSIONS: aPL show a low prevalence in COVID-19 patients and are not associated with major thrombotic events. aPL in COVID-19 patients are mainly directed against β(2)GPI but display an epitope specificity different from antibodies in antiphospholipid syndrome. url: https://doi.org/10.3389/fimmu.2020.584241 doi: 10.3389/fimmu.2020.584241 id: cord-350836-1enteev7 author: Brisse, Morgan title: Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5 date: 2019-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RIG-I (Retinoic acid-inducible gene I) and MDA5 (Melanoma Differentiation-Associated protein 5), collectively known as the RIG-I-like receptors (RLRs), are key protein sensors of the pathogen-associated molecular patterns (PAMPs) in the form of viral double-stranded RNA (dsRNA) motifs to induce expression of type 1 interferons (IFN1) (IFNα and IFNβ) and other pro-inflammatory cytokines during the early stage of viral infection. While RIG-I and MDA5 share many genetic, structural and functional similarities, there is increasing evidence that they can have significantly different strategies to recognize different pathogens, PAMPs, and in different host species. This review article discusses the similarities and differences between RIG-I and MDA5 from multiple perspectives, including their structures, evolution and functional relationships with other cellular proteins, their differential mechanisms of distinguishing between host and viral dsRNAs and interactions with host and viral protein factors, and their immunogenic signaling. A comprehensive comparative analysis can help inform future studies of RIG-I and MDA5 in order to fully understand their functions in order to optimize potential therapeutic approaches targeting them. url: https://doi.org/10.3389/fimmu.2019.01586 doi: 10.3389/fimmu.2019.01586 id: cord-278081-tk7vn1v1 author: Brooks, Wesley H. title: Viral Impact in Autoimmune Diseases: Expanding the “X Chromosome–Nucleolus Nexus” Hypothesis date: 2017-11-28 words: 9823.0 sentences: 457.0 pages: flesch: 42.0 cache: ./cache/cord-278081-tk7vn1v1.txt txt: ./txt/cord-278081-tk7vn1v1.txt summary: Here is presented new details to the hypothesis, explaining how the disrupted chromatin can lead to subsequent disruption of the nucleolus, even nucleolar fragmentation, which results in ineffective nucleolar functioning, misfolded RNAs, misassembled or incompletely assembled ribonucleoprotein (RNP) complexes, and stabilization of nucleolar components in autoantigenic conformations. For now there is no direct connection between viruses and the "X chromosome-nucleolus nexus" hypothesis to the increased risk of cancers among autoimmune disease patients but we can consider the induction by viruses of increased polyamine levels and the possible reactivation of X-linked polyamine genes as means by which competition for the cellular methyl donor, SAM, could reduce DNA methylation and open oncogenes for overexpression in proliferation competent cells. A disrupted Barr body could generate an abundance of polyamines and Alu RNA from X-linked genes and elements that further stress and damage the nucleolus, making it very inefficient in its functions, even fragmenting it and possibly leading to cell death. abstract: Viruses are suspected of significant roles in autoimmune diseases but the mechanisms are unclear. We get some insight by considering demands a virus places on host cells. Viruses not only require production of their own proteins, RNA and/or DNA, but also production of additional cellular machinery, such as ribosomes, to handle the increased demands. Since the nucleolus is a major site of RNA processing and ribonucleoprotein assembly, nucleoli are targeted by viruses, directly when viral RNA and proteins enter the nucleolus and indirectly when viruses induce increased expression of cellular polyamine genes. Polyamines are at high levels in nucleoli to assist in RNA folding. The size and activity of nucleoli increase directly with increases in polyamines. Nucleolar expansion due to abnormal increases in polyamines could disrupt nearby chromatin, such as the inactive X chromosome, leading to expression of previously sequestered DNA. Sudden expression of a large concentration of Alu elements from the disrupted inactive X can compete with RNA transcripts containing intronic Alu sequences that normally maintain nucleolar structural integrity. Such disruption of nucleolar activity can lead to misfolded RNAs, misassembled ribonucleoprotein complexes, and fragmentation of the nucleolus. Many autoantigens in lupus are, at least transiently, components of the nucleolus. Considering these effects of viruses, the “X chromosome–nucleolus nexus” hypothesis, which proposed disruption of the inactive X by the nucleolus during stress, is now expanded here to propose subsequent disruption of the nucleolus by previously sequestered Alu elements, which can fragment the nucleolus, leading to generation of autoantigens. url: https://doi.org/10.3389/fimmu.2017.01657 doi: 10.3389/fimmu.2017.01657 id: cord-257662-viy65y72 author: Burrack, Kristina S. title: The Role of Myeloid Cell Activation and Arginine Metabolism in the Pathogenesis of Virus-Induced Diseases date: 2014-09-08 words: 9002.0 sentences: 391.0 pages: flesch: 33.0 cache: ./cache/cord-257662-viy65y72.txt txt: ./txt/cord-257662-viy65y72.txt summary: Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). In this review, we highlight recent studies of viral infections where myeloid cell polarization -resulting in expression of iNOS or Arg1 -contribute to viral control or the development of chronic virus infection and mediate the resolution of tissue damage or cause immunopathology. It was further shown that genetic deletion of myeloid cell Arg1 resulted in enhanced viral control in inflamed muscle tissue and reduced tissue pathology following RRV infection in mice (69) , suggesting an important role for Arg1-expressing macrophages in the persistence of these chronic viruses. In the absence of iNKT cells, influenza A (PR/8 strain) infection was shown to induce the expansion of CD11b + GR-1 + MDSCs in the lungs of mice, which suppressed influenza-specific T cell and antibody responses through the activity of both arginase and NOS, resulting in higher viral titers and increased mortality (81) . abstract: When an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/25250029/ doi: 10.3389/fimmu.2014.00428 id: cord-297960-4x1j0iqg author: Bösl, Korbinian title: Common Nodes of Virus–Host Interaction Revealed Through an Integrated Network Analysis date: 2019-10-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Viruses are one of the major causes of acute and chronic infectious diseases and thus a major contributor to the global burden of disease. Several studies have shown how viruses have evolved to hijack basic cellular pathways and evade innate immune response by modulating key host factors and signaling pathways. A collective view of these multiple studies could advance our understanding of virus-host interactions and provide new therapeutic perspectives for the treatment of viral diseases. Here, we performed an integrative meta-analysis to elucidate the 17 different host-virus interactomes. Network and bioinformatics analyses showed how viruses with small genomes efficiently achieve the maximal effect by targeting multifunctional and highly connected host proteins with a high occurrence of disordered regions. We also identified the core cellular process subnetworks that are targeted by all the viruses. Integration with functional RNA interference (RNAi) datasets showed that a large proportion of the targets are required for viral replication. Furthermore, we performed an interactome-informed drug re-purposing screen and identified novel activities for broad-spectrum antiviral agents against hepatitis C virus and human metapneumovirus. Altogether, these orthogonal datasets could serve as a platform for hypothesis generation and follow-up studies to broaden our understanding of the viral evasion landscape. url: https://doi.org/10.3389/fimmu.2019.02186 doi: 10.3389/fimmu.2019.02186 id: cord-346389-gbmnoo84 author: Callender, Lauren A. title: The Impact of Pre-existing Comorbidities and Therapeutic Interventions on COVID-19 date: 2020-08-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Evidence from the global outbreak of SARS-CoV-2 has clearly demonstrated that individuals with pre-existing comorbidities are at a much greater risk of dying from COVID-19. This is of great concern for individuals living with these conditions, and a major challenge for global healthcare systems and biomedical research. Not all comorbidities confer the same risk, however, many affect the function of the immune system, which in turn directly impacts the response to COVID-19. Furthermore, the myriad of drugs prescribed for these comorbidities can also influence the progression of COVID-19 and limit additional treatment options available for COVID-19. Here, we review immune dysfunction in response to SARS-CoV-2 infection and the impact of pre-existing comorbidities on the development of COVID-19. We explore how underlying disease etiologies and common therapies used to treat these conditions exacerbate COVID-19 progression. Moreover, we discuss the long-term challenges associated with the use of both novel and repurposed therapies for the treatment of COVID-19 in patients with pre-existing comorbidities. url: https://www.ncbi.nlm.nih.gov/pubmed/32903476/ doi: 10.3389/fimmu.2020.01991 id: cord-262575-06i2nv0t author: Caracciolo, Massimo title: Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome date: 2020-08-25 words: 2163.0 sentences: 139.0 pages: flesch: 40.0 cache: ./cache/cord-262575-06i2nv0t.txt txt: ./txt/cord-262575-06i2nv0t.txt summary: title: Case Report: Canakinumab for the Treatment of a Patient With COVID-19 Acute Respiratory Distress Syndrome Severe cases of COVID-19 present with serious lung inflammation, acute respiratory distress syndrome and multiorgan damage. SARS-CoV-2 infection is associated with high cytokine levels, including interleukin-6 and certain subsets of immune cells, in particular, NK, distinguished according to the cell surface density of CD56. Cytokine levels are inversely correlated with lymphocyte count, therefore cytokine release syndrome may be an impediment to the adaptive immune response against SARS-CoV-2 infection. An 85 year old male presenting in our hospital with COVID-19, whose condition was complicated by acute respiratory distress syndrome and cardiac and renal failure (with oliguria) after 25 days of hospitalization, was intubated and received canakinumab for compassionate use. The immune response, including the release of pro-inflammatory cytokines and activation of T cells, are essential for controlling the viral spread, inflammation, and tissue renewal (5, 6) . abstract: Severe cases of COVID-19 present with serious lung inflammation, acute respiratory distress syndrome and multiorgan damage. SARS-CoV-2 infection is associated with high cytokine levels, including interleukin-6 and certain subsets of immune cells, in particular, NK, distinguished according to the cell surface density of CD56. Cytokine levels are inversely correlated with lymphocyte count, therefore cytokine release syndrome may be an impediment to the adaptive immune response against SARS-CoV-2 infection. Canakinumab, a monoclonal antibody targeting IL-1β is under investigation for the treatment of severe SAR-CoV-2 infection. An 85 year old male presenting in our hospital with COVID-19, whose condition was complicated by acute respiratory distress syndrome and cardiac and renal failure (with oliguria) after 25 days of hospitalization, was intubated and received canakinumab for compassionate use. On the next day, diuresis recovered and conditions improved: high IL-6 levels and NK cells expressing CD56(bright) (associated with cytokine relase) were significantly reduced giving rise to NK CD56(dim). Patient died on day 58 with pulmonary bacterial superinfection and persistent SARS-CoV-2 positivity. In conclusion, canakinumab rescued a high risk, very elderly patient, from multiorgan damage complicating COVID-19. It may represent an useful treatment in severe cases. url: https://doi.org/10.3389/fimmu.2020.01942 doi: 10.3389/fimmu.2020.01942 id: cord-340475-h0q1m3ed author: Carnero, Elena title: Type I Interferon Regulates the Expression of Long Non-Coding RNAs date: 2014-11-06 words: 10164.0 sentences: 544.0 pages: flesch: 55.0 cache: ./cache/cord-340475-h0q1m3ed.txt txt: ./txt/cord-340475-h0q1m3ed.txt summary: Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response.These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. HuH7 cells were treated for 6, 24, 48, or 72 h with increasing doses of IFNα2 up to 10,000 units/ml, and the expression levels of GBP1, IRF1, BST2, OAS, IL6, and ISG15 were evaluated by qRT-PCR (Figure 1) . abstract: Interferons (IFNs) are key players in the antiviral response. IFN sensing by the cell activates transcription of IFN-stimulated genes (ISGs) able to induce an antiviral state by affecting viral replication and release. IFN also induces the expression of ISGs that function as negative regulators to limit the strength and duration of IFN response. The ISGs identified so far belong to coding genes. However, only a small proportion of the transcriptome corresponds to coding transcripts and it has been estimated that there could be as many coding as long non-coding RNAs (lncRNAs). To address whether IFN can also regulate the expression of lncRNAs, we analyzed the transcriptome of HuH7 cells treated or not with IFNα2 by expression arrays. Analysis of the arrays showed increased levels of several well-characterized coding genes that respond to IFN both at early or late times. Furthermore, we identified several IFN-stimulated or -downregulated lncRNAs (ISRs and IDRs). Further validation showed that ISR2, 8, and 12 expression mimics that of their neighboring genes GBP1, IRF1, and IL6, respectively, all related to the IFN response. These genes are induced in response to different doses of IFNα2 in different cell lines at early (ISR2 or 8) or later (ISR12) time points. IFNβ also induced the expression of these lncRNAs. ISR2 and 8 were also induced by an influenza virus unable to block the IFN response but not by other wild-type lytic viruses tested. Surprisingly, both ISR2 and 8 were significantly upregulated in cultured cells and livers from patients infected with HCV. Increased levels of ISR2 were also detected in patients chronically infected with HIV. This is relevant as genome-wide guilt-by-association studies predict that ISR2, 8, and 12 may function in viral processes, in the IFN pathway and the antiviral response. Therefore, we propose that these lncRNAs could be induced by IFN to function as positive or negative regulators of the antiviral response. url: https://www.ncbi.nlm.nih.gov/pubmed/25414701/ doi: 10.3389/fimmu.2014.00548 id: cord-350041-b1vmnwv2 author: Cena, Hellas title: Coronavirus Disease (COVID-19–SARS-CoV-2) and Nutrition: Is Infection in Italy Suggesting a Connection? date: 2020-05-07 words: 3017.0 sentences: 147.0 pages: flesch: 35.0 cache: ./cache/cord-350041-b1vmnwv2.txt txt: ./txt/cord-350041-b1vmnwv2.txt summary: There has been a gradual increase in studies exploring prevention and control measures, and we recommend paying close attention to nutrition, which may contribute to modulating some important consequences of COVID-19 infection, as such pro-inflammatory cytokine storm. Unfortunately, we do not yet have weight, height, and waist circumference data for all patients with laboratory-confirmed COVID-19, and, therefore, we cannot disentangle the effects of adiposity on lung function and immune response to viral infection. Recent data on patients with laboratory-confirmed COVID-19 treated at an academic health institution in New York City, the epicenter of the COVID-19 outbreak in the United States, between March 1, 2020, and April 2, 2020, with follow up through April 7, 2020 (13, 14) showed that obesity, after age, was linked to more severe coronavirus cases, with a substantially higher odds ratio than any cardiovascular or pulmonary disease. abstract: Novel coronavirus disease (COVID-19) was declared a global pandemic on March 11, 2020. The outbreak first occurred in Wuhan, Hubei, China, in December 2019 and hit Italy heavily in February 2020. Several countries are adopting complete or partial lockdown to contain the growth of COVID-19 infection. These measures may affect people's mental health and well-being but are necessary to avoid spreading the pandemic. There has been a gradual increase in studies exploring prevention and control measures, and we recommend paying close attention to nutrition, which may contribute to modulating some important consequences of COVID-19 infection, as such pro-inflammatory cytokine storm. url: https://www.ncbi.nlm.nih.gov/pubmed/32574257/ doi: 10.3389/fimmu.2020.00944 id: cord-304619-tpv76833 author: Chatterjea, Devavani title: Teaching Immunology as a Liberal Art date: 2020-07-14 words: 3322.0 sentences: 135.0 pages: flesch: 41.0 cache: ./cache/cord-304619-tpv76833.txt txt: ./txt/cord-304619-tpv76833.txt summary: A complex, rapidly evolving biomedical field that is of critical relevance to human health and well-being, immunology provides important and substantive opportunities to practice and teach the central tenets of a liberal arts curriculum. Iteratively learning to read the often dense and technical immunological literature and synthesizing and communicating these findings in their own written and spoken words is both preparation for future work in biomedical fields and a core tenet of a liberal arts education-the importance of listening, reading, speaking, arguing, and writing. However, they also write white papers and reflective essays connecting their learning in immunology to other disciplines, prepare educational materials for community organizations, teach secondary school students and mentor younger peers and, in doing so, practice translating the technical jargon of scientific communication into information that their audiences need and can use. Teaching about our immune systems in integrative, socially relevant ways can help our students make meaningful connections between the content of their learning and the larger global context in which they live. abstract: A complex, rapidly evolving biomedical field that is of critical relevance to human health and well-being, immunology provides important and substantive opportunities to practice and teach the central tenets of a liberal arts curriculum. url: https://doi.org/10.3389/fimmu.2020.01462 doi: 10.3389/fimmu.2020.01462 id: cord-034310-izpt032p author: Chernomordik, Fernando title: The Role of T Cells Reactive to the Cathelicidin Antimicrobial Peptide LL-37 in Acute Coronary Syndrome and Plaque Calcification date: 2020-10-06 words: 5966.0 sentences: 306.0 pages: flesch: 46.0 cache: ./cache/cord-034310-izpt032p.txt txt: ./txt/cord-034310-izpt032p.txt summary: Furthermore, studies in apoE−/− mice suggest that T cells reactive to mCRAMP are functionally active in atherosclerosis and may be involved in modulating plaque calcification. Given the role of anti-microbial peptides as potential selfantigens in atherosclerosis, and the possible association with acute events, we tested if the cleaved fragment of hCAP-18, the cationic antimicrobial peptide LL-37, would induce differential T cell immune responses in patients with ACS. In this study, we showed that: (a) LL-37 stimulation of PBMCs from patients with ACS induced the persistence of CD8+ TEM cell response compared to patients with stable CAD or selfreported controls; (b) Immunization of apoE−/− mice with mCRAMP, the cationic fragment of CRAMP, increased CD8 CM T cell activation and cytolytic activity; and (c) Adoptive transfer of T cells from mice immunized with mCRAMP was associated with smaller atherosclerotic aortic plaque area, and absence of aortic sinus plaque calcification. abstract: The human cationic anti-microbial peptide LL-37 is a T cell self-antigen in patients with psoriasis, who have increased risk of cardiovascular events. However, the role of LL-37 as a T cell self-antigen in the context of atherosclerosis remains unclear. The objective of this study was to test for the presence of T cells reactive to LL-37 in patients with acute coronary syndrome (ACS). Furthermore, the role of T cells reactive to LL-37 in atherosclerosis was assessed using apoE−/− mice immunized with the LL-37 mouse ortholog, mCRAMP. Peripheral blood mononuclear cells (PBMCs) from patients with ACS were stimulated with LL-37. PBMCs from stable coronary artery disease (CAD) patients or self-reported subjects served as controls. T cell memory responses were analyzed with flow cytometry. Stimulation of PBMCs with LL-37 reduced CD8+ effector T cell responses in controls and patients with stable CAD but not in ACS and was associated with reduced programmed cell death protein 1 (PDCD1) mRNA expression. For the mouse studies, donor apoE−/− mice were immunized with mCRAMP or adjuvant as controls, then T cells were isolated and adoptively transferred into recipient apoE−/− mice fed a Western diet. Recipient mice were euthanized after 5 weeks. Whole aortas and hearts were collected for analysis of atherosclerotic plaques. Spleens were collected for flow cytometric and mRNA expression analysis. Adoptive transfer experiments in apoE−/− mice showed a 28% reduction in aortic plaque area in mCRAMP T cell recipient mice (P < 0.05). Fifty six percent of adjuvant T cell recipient mice showed calcification in atherosclerotic plaques, compared to none in the mCRAMP T cell recipient mice (Fisher’s exact test P = 0.003). Recipients of T cells from mice immunized with mCRAMP had increased IL-10 and IFN-γ expression in CD8+ T cells compared to controls. In conclusion, the persistence of CD8+ effector T cell response in PBMCs from patients with ACS stimulated with LL-37 suggests that LL-37-reactive T cells may be involved in the acute event. Furthermore, studies in apoE−/− mice suggest that T cells reactive to mCRAMP are functionally active in atherosclerosis and may be involved in modulating plaque calcification. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573569/ doi: 10.3389/fimmu.2020.575577 id: cord-282336-zvc04s39 author: Choudhary, Ishita title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 words: 7910.0 sentences: 405.0 pages: flesch: 48.0 cache: ./cache/cord-282336-zvc04s39.txt txt: ./txt/cord-282336-zvc04s39.txt summary: In contrast, the lung injury in LPS-challenged TTP KO mice was characterized by severe consolidation (>90% of total area of lung section) (Figures 1F,G) that included infiltration of neutrophils, edema, fibrin, and airspace hemorrhage within the airway and alveolar lumen, multifocal loss of bronchiolar epithelium with infiltration of neutrophils and red blood cells within the bronchiolar lumen, and moderate to severe perivascular edema and inflammation (Figures 1F-H) . To determine the cell-specific role of TTP levels in ALI, we modulated TTP levels in hematopoietic progenitor cells (HPCs) and non-HPCs. In order to test whether donor HPCs repopulate the recipient mouse lungs, we first made bone marrow chimeras in which total body irradiated WT mice were transplanted with HPCs from a mouse expressing green fluorescent protein (GFP) in their somatic cells. abstract: Tristetraprolin (TTP) is a mRNA binding protein that binds to adenylate-uridylate-rich elements within the 3′ untranslated regions of certain transcripts, such as tumor necrosis factor (Tnf) mRNA, and increases their rate of decay. Modulation of TTP expression is implicated in inflammation; however, its role in acute lung inflammation remains unknown. Accordingly, we tested the role of TTP in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LPS-challenged TTP-knockout (TTP(KO)) mice, as well as myeloid cell-specific TTP-deficient (TTP(myeKO)) mice, exhibited significant increases in lung injury, although these responses were more robust in the TTP(KO). Mice with systemic overexpression of TTP (TTP(ΔARE)) were protected from ALI, as indicated by significantly reduced neutrophilic infiltration, reduced levels of neutrophil chemoattractants, and histological parameters of ALI. Interestingly, while irradiated wild-type (WT) mice reconstituted with TTP(KO) hematopoietic progenitor cells (HPCs) showed exaggerated ALI, their reconstitution with the TTP(ΔARE) HPCs mitigated ALI. The reconstitution of irradiated TTP(ΔARE) mice with HPCs from either WT or TTP(ΔARE) donors conferred significant protection against ALI. In contrast, irradiated TTP(ΔARE) mice reconstituted with TTP(KO) HPCs had exaggerated ALI, but the response was milder as compared to WT recipients that received TTP(KO) HPCs. Finally, the reconstitution of irradiated TTP(KO) recipient mice with TTP(ΔARE) HPCs did not confer any protection to the TTP(KO) mice. These data together suggest that non-HPCs-specific overexpression of TTP within the lungs protects against ALI via downregulation of neutrophil chemoattractants and reduction in neutrophilic infiltration. url: https://doi.org/10.3389/fimmu.2020.02164 doi: 10.3389/fimmu.2020.02164 id: cord-285760-y37ji92k author: Connell, Anna R. title: Mumps Outbreaks in Vaccinated Populations—Is It Time to Re-assess the Clinical Efficacy of Vaccines? date: 2020-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: History illustrates the remarkable public health impact of mass vaccination, by dramatically improving life expectancy and reducing the burden of infectious diseases and co-morbidities worldwide. It has been perceived that if an individual adhered to the MMR vaccine schedule that immunity to mumps virus (MuV) would be lifelong. Recent mumps outbreaks in individuals who had received two doses of the Measles Mumps Rubella (MMR) vaccine has challenged the efficacy of the MMR vaccine. However, clinical symptoms, complications, viral shedding and transmission associated with mumps infection has been shown to be reduced in vaccinated individuals, demonstrating a benefit of this vaccine. Therefore, the question of what constitutes a good mumps vaccine and how its impact is assessed in this modern era remains to be addressed. Epidemiology of the individuals most affected by the outbreaks (predominantly young adults) and variance in the circulating MuV genotype have been well-described alluding to a collection of influences such as vaccine hesitancy, heterogeneous vaccine uptake, primary, and/or secondary vaccine failures. This review aims to discuss in detail the interplay of factors thought to be contributing to the current mumps outbreaks seen in highly vaccinated populations. In addition, how mumps diagnoses has progressed and impacted the understanding of mumps infection since a mumps vaccine was first developed, the limitations of current laboratory tests in confirming protection in vaccinated individuals and how vaccine effectiveness is quantified are also considered. By highlighting knowledge gaps within this area, this state-of-the-art review proposes a change of perspective regarding the impact of a vaccine in a highly vaccinated population from a clinical, diagnostic and public perspective, highlighting a need for a paradigm shift on what is considered vaccine immunity. url: https://www.ncbi.nlm.nih.gov/pubmed/33072071/ doi: 10.3389/fimmu.2020.02089 id: cord-266085-914y3je0 author: Correa, Isabel title: Evaluation of Antigen-Conjugated Fluorescent Beads to Identify Antigen-Specific B Cells date: 2018-03-23 words: 6893.0 sentences: 282.0 pages: flesch: 42.0 cache: ./cache/cord-266085-914y3je0.txt txt: ./txt/cord-266085-914y3je0.txt summary: To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. In our study, we present an antigen-conjugated fluorescent bead methodology designed to identify and isolate single antibody-expressing cells and to derive and clone matched heavy and light chain antibody variable regions into full length antibodies. The workflow features bead-based identification and isolation of specific B cells using direct fluorescent-activated cell sorting, sequencing, and cloning of matched heavy and light chain variable regions in a single full sequence antibody expression vector system, and expression and testing the antigenic reactivity of the antibody clone. Following flow sorting of single cells directly into lysis buffer, we confirmed that it is possible to extract matched H and L chain variable region sequences from single antibody-expressing cells selected by specific antigen-coated beads. abstract: Selection of single antigen-specific B cells to identify their expressed antibodies is of considerable interest for evaluating human immune responses. Here, we present a method to identify single antibody-expressing cells using antigen-conjugated fluorescent beads. To establish this, we selected Folate Receptor alpha (FRα) as a model antigen and a mouse B cell line, expressing both the soluble and the membrane-bound forms of a human/mouse chimeric antibody (MOv18 IgG1) specific for FRα, as test antibody-expressing cells. Beads were conjugated to FRα using streptavidin/avidin-biotin bridges and used to select single cells expressing the membrane-bound form of anti-FRα. Bead-bound cells were single cell-sorted and processed for single cell RNA retrotranscription and PCR to isolate antibody heavy and light chain variable regions. Variable regions were then cloned and expressed as human IgG1/k antibodies. Like the original clone, engineered antibodies from single cells recognized native FRα. To evaluate whether antigen-coated beads could identify specific antibody-expressing cells in mixed immune cell populations, human peripheral blood mononuclear cells (PBMCs) were spiked with test antibody-expressing cells. Antigen-specific cells could comprise up to 75% of cells selected with antigen-conjugated beads when the frequency of the antigen-positive cells was 1:100 or higher. In PBMC pools, beads conjugated to recombinant antigens FRα and HER2 bound antigen-specific anti-FRα MOv18 and anti-HER2 Trastuzumab antibody-expressing cells, respectively. From melanoma patient-derived B cells selected with melanoma cell line-derived protein-coated fluorescent beads, we generated a monoclonal antibody that recognized melanoma antigen-coated beads. This approach may be further developed to facilitate analysis of B cells and their antibody profiles at the single cell level and to help unravel humoral immune repertoires. url: https://www.ncbi.nlm.nih.gov/pubmed/29628923/ doi: 10.3389/fimmu.2018.00493 id: cord-283382-t890r7xp author: Coughlan, Lynda title: Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines date: 2020-05-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Adenoviral vectors are a safe and potently immunogenic vaccine delivery platform. Non-replicating Ad vectors possess several attributes which make them attractive vaccines for infectious disease, including their capacity for high titer growth, ease of manipulation, safety, and immunogenicity in clinical studies, as well as their compatibility with clinical manufacturing and thermo-stabilization procedures. In general, Ad vectors are immunogenic vaccines, which elicit robust transgene antigen-specific cellular (namely CD8(+) T cells) and/or humoral immune responses. A large number of adenoviruses isolated from humans and non-human primates, which have low seroprevalence in humans, have been vectorized and tested as vaccines in animal models and humans. However, a distinct hierarchy of immunological potency has been identified between diverse Ad vectors, which unfortunately limits the potential use of many vectors which have otherwise desirable manufacturing characteristics. The precise mechanistic factors which underlie the profound disparities in immunogenicity are not clearly defined and are the subject of ongoing, detailed investigation. It has been suggested that a combination of factors contribute to the potent immunogenicity of particular Ad vectors, including the magnitude and duration of vaccine antigen expression following immunization. Furthermore, the excessive induction of Type I interferons by some Ad vectors has been suggested to impair transgene expression levels, dampening subsequent immune responses. Therefore, the induction of balanced, but not excessive stimulation of innate signaling is optimal. Entry factor binding or receptor usage of distinct Ad vectors can also affect their in vivo tropism following administration by different routes. The abundance and accessibility of innate immune cells and/or antigen-presenting cells at the site of injection contributes to early innate immune responses to Ad vaccination, affecting the outcome of the adaptive immune response. Although a significant amount of information exists regarding the tropism determinants of the common human adenovirus type-5 vector, very little is known about the receptor usage and tropism of rare species or non-human Ad vectors. Increased understanding of how different facets of the host response to Ad vectors contribute to their immunological potency will be essential for the development of optimized and customized Ad vaccine platforms for specific diseases. url: https://doi.org/10.3389/fimmu.2020.00909 doi: 10.3389/fimmu.2020.00909 id: cord-352737-3ttrx3lf author: Cunha, Lucas Leite title: Remodeling of the Immune Response With Aging: Immunosenescence and Its Potential Impact on COVID-19 Immune Response date: 2020-08-07 words: 6824.0 sentences: 337.0 pages: flesch: 37.0 cache: ./cache/cord-352737-3ttrx3lf.txt txt: ./txt/cord-352737-3ttrx3lf.txt summary: Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. Interestingly, polymorphonuclear leucocytes from the elderly are less capable of modulating the triggering receptor expressed on myeloid cell-1 (TREM-1)-induced oxidative bursts, suggesting that TREM-1 signal transduction altered with aging may be one of the mediators of the decrease in microbicidal potential of innate immune cells in older adults (41) . abstract: Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32849623/ doi: 10.3389/fimmu.2020.01748 id: cord-336201-fl606l3b author: Daryabor, Gholamreza title: The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System date: 2020-07-22 words: 13863.0 sentences: 715.0 pages: flesch: 38.0 cache: ./cache/cord-336201-fl606l3b.txt txt: ./txt/cord-336201-fl606l3b.txt summary: Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. T2DM, the most common form of diabetes (∼90%), is characterized by a systemic inflammatory disease accompanied by insulin resistance (IR) or decreased metabolic response to insulin in several tissues, including the adipose tissue, liver, and skeletal muscle, as well as by reduced insulin synthesis by pancreatic beta cells (4, 5) . During the progression of diabetes, hyperglycemia promotes mitochondrial dysfunction and induces the formation of reactive oxygen species (ROS) that cause oxidative stress in several tissues such as blood vessels and pancreatic beta cells (7) (8) (9) . In addition, the attachment of AGEs to their receptors [e.g., CD36, galectin-3, scavenger receptors types I (SR-A1), and II (SR-A2)] on the surfaces of immune cells in the circulation and tissues activates the expression of pro-inflammatory cytokines and increases free radical generation (18) . abstract: Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/32793223/ doi: 10.3389/fimmu.2020.01582 id: cord-332150-j76726no author: De Stefano, Ludovico title: A “Window of Therapeutic Opportunity” for Anti-Cytokine Therapy in Patients With Coronavirus Disease 2019 date: 2020-10-06 words: 3616.0 sentences: 166.0 pages: flesch: 28.0 cache: ./cache/cord-332150-j76726no.txt txt: ./txt/cord-332150-j76726no.txt summary: The main challenge for effective administration of anti-cytokine therapy in COVID-19 will be therefore to better define a precise "window of therapeutic opportunity." Only considering a more specific set of criteria able to integrate information on direct viral damage, the cytokine burden, and the patient''s immune vulnerability, it will be possible to decide, carefully balancing both benefits and risks, the appropriateness of using immunosuppressive drugs even in patients affected primarily by an infectious disease. Discovery of virus and host genomic factors will undoubtedly support risk stratification and targeted treatment; however, as genomic studies require long times before entering clinical practice, it is urgent to integrate easily accessible information on the dynamics and pathogenicity of the immune response during the different phases of SARS-CoV-2 infection. Accordingly, longitudinal immune profiling of hospitalized COVID-19 cases with different outcomes has recently shown that, despite similar levels of inflammatory cytokines in the first 10 days from symptom onset, patients with less severe disease evolution also express mediators of wound healing and tissue repair (41) . abstract: The effects of cytokine inhibition in the different phases of the severe coronavirus disease 2019 (COVID-19) are currently at the center of intense debate, and preliminary results from observational studies and case reports offer conflicting results thus far. The identification of the correct timing of administration of anti-cytokine therapies and other immunosuppressants in COVID-19 should take into account the intricate relationship between the viral burden, the hyperactivation of the innate immune system and the adaptive immune dysfunction. The main challenge for effective administration of anti-cytokine therapy in COVID-19 will be therefore to better define a precise “window of therapeutic opportunity.” Only considering a more specific set of criteria able to integrate information on direct viral damage, the cytokine burden, and the patient’s immune vulnerability, it will be possible to decide, carefully balancing both benefits and risks, the appropriateness of using immunosuppressive drugs even in patients affected primarily by an infectious disease. url: https://doi.org/10.3389/fimmu.2020.572635 doi: 10.3389/fimmu.2020.572635 id: cord-352150-ey9kc7zj author: Degauque, Nicolas title: Cross-Reactivity of TCR Repertoire: Current Concepts, Challenges, and Implication for Allotransplantation date: 2016-03-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Being able to track donor reactive T cells during the course of organ transplantation is a key to improve the graft survival, to prevent graft dysfunction, and to adapt the immunosuppressive regimen. The attempts of transplant immunologists have been for long hampered by the large size of the alloreactive T cell repertoire. Understanding how self-TCR can interact with allogeneic MHC is a key to critically appraise the different assays available to analyze the TCR Vβ repertoire usage. In this report, we will review conceptually and experimentally the process of cross-reactivity. We will then highlight what can be learned from allotransplantation, a situation of artificial cross-reactivity. Finally, the low- and high-resolution techniques to characterize the TCR Vβ repertoire usage in transplantation will be critically discussed. url: https://doi.org/10.3389/fimmu.2016.00089 doi: 10.3389/fimmu.2016.00089 id: cord-003724-705h5l06 author: Di Lullo, Giulia title: Identification of a Novel Non-desmoglein Autoantigen in Pemphigus Vulgaris date: 2019-06-19 words: 4132.0 sentences: 191.0 pages: flesch: 38.0 cache: ./cache/cord-003724-705h5l06.txt txt: ./txt/cord-003724-705h5l06.txt summary: Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The existence of both pathogenic and non-pathogenic anti-Dsg autoAbs has recently been underscored by isolation of human monoclonal antibodies (hMabs) from pemphigus patients. Then, considering that previous studies demonstrated the ability of intact autoAbs to enter living cells (8, 16, 17) , we addressed the potential pathogenicity of α-catenin-specific Mab PVF144 by evaluating its acantholytic activity in an in vitro keratinocyte dissociation assay. Further studies are needed: (i) to evaluate whether PVF144 may act synergistically with anti-Dsg antibodies using more informative approaches, such as in vitro organ culture or in vivo models; (ii) to assess the possible role of anti-α-catenin autoAbs in pemphigus initiation and evolution in vivo; and (iii) to characterize this novel antigen as a possible target of epitope spreading phenomena in PV. abstract: Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied a previously developed method for the efficient immortalization of IgG+ memory B cells to identify novel target antigens in PV. A human monoclonal antibody reactive with a hitherto unreported non-Dsg antigen was isolated. Immunoprecipitation and immunoblotting studies with keratinocyte extracts indicated α-catenin as the putative antigen, then confirmed by immunoblotting on the recombinant protein. Four of ten PV sera reacted with recombinant α-catenin. Although the isolated human monoclonal antibody was per se unable to dissociate keratinocyte monolayers and also to synergize with a pathogenic antibody in vitro, further studies are warranted to assess its possible in vivo contribution in the multifactorial pathogenesis and heterogeneous manifestations of PV disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593111/ doi: 10.3389/fimmu.2019.01391 id: cord-333932-aqcllik0 author: Diao, Bo title: Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19) date: 2020-05-01 words: 3822.0 sentences: 179.0 pages: flesch: 50.0 cache: ./cache/cord-333932-aqcllik0.txt txt: ./txt/cord-333932-aqcllik0.txt summary: Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. Our results thus provide a preliminary demonstration of T cell exhaustion during COVID-19 infection and suggest that more urgent, early intervention may be required in patients with low T lymphocyte counts. The expression of angiotensin converting enzyme 2 (ACE2), the predicted receptor of SARS-CoV-2 viruses, is absent on T cells (11) , suggesting that the depressed T counts in COVID-19 patients mentioned above (Figure 1 ) were likely not caused by direct infection of T cells. We demonstrate here that COVID-19 patients have very high levels of serum IL-10 following SARS-CoV-2 infection, while also displaying high levels of the PD-1 and Tim-3 exhaustion markers on their T cells, suggesting that IL-10 might be mechanistically responsible. abstract: Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: We retrospectively reviewed the counts of T cells and serum cytokine concentration from data of 522 patients with laboratory-confirmed COVID-19 and 40 healthy controls. In addition, the expression of T cell exhaustion markers were measured in 14 COVID-19 cases. Results: The number of total T cells, CD4(+) and CD8(+) T cells were dramatically reduced in COVID-19 patients, especially in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8(+) T cells or CD4(+) T cells lower than 800, 300, or 400/μL, respectively, were negatively correlated with patient survival. T cell numbers were negatively correlated to serum IL-6, IL-10, and TNF-α concentration, with patients in the disease resolution period showing reduced IL-6, IL-10, and TNF-α concentrations and restored T cell counts. T cells from COVID-19 patients had significantly higher levels of the exhausted marker PD-1. Increasing PD-1 and Tim-3 expression on T cells was seen as patients progressed from prodromal to overtly symptomatic stages. Conclusions: T cell counts are reduced significantly in COVID-19 patients, and the surviving T cells appear functionally exhausted. Non-ICU patients with total T cells counts lower than 800/μL may still require urgent intervention, even in the immediate absence of more severe symptoms due to a high risk for further deterioration in condition. url: https://www.ncbi.nlm.nih.gov/pubmed/32425950/ doi: 10.3389/fimmu.2020.00827 id: cord-354030-8tfg881h author: Dong, Rong title: Contriving Multi-Epitope Subunit of Vaccine for COVID-19: Immunoinformatics Approaches date: 2020-07-28 words: 7983.0 sentences: 442.0 pages: flesch: 52.0 cache: ./cache/cord-354030-8tfg881h.txt txt: ./txt/cord-354030-8tfg881h.txt summary: The realm of immunoinformatics tools considers the mechanism of the host immune response to yield additional methodologies in the design of vaccine against diseases are cost-effective and convenient, as in silico predictions can reduce the number of experiments needed (13, 14) . In this present, we employed immunoinformatics to predict multiple immunogenic proteins from the SARS-CoV-2 proteome and thereby design a multi-epitope vaccine. developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . developed a multi-epitope vaccine that was designed using immunoinformatics tools that potentially trigger both CD4+ and CD8+ T-cell immune responses (16) . A vaccine based on the spike protein could induce antibodies to block SARS-COV-2 binding and fusion or neutralize virus infection (18) , as well as induce harmful immune responses that cause liver damage (19) . To design an effective vaccine, we selected the SARS-CoV-2 protein through the above-mentioned methods for epitope prediction. Development of epitope-based peptide vaccine against novel coronavirus 2019 (SARS-COV-2): Immunoinformatics approach abstract: COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1–14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections. url: https://doi.org/10.3389/fimmu.2020.01784 doi: 10.3389/fimmu.2020.01784 id: cord-003122-a3f4l6iu author: Dou, Dan title: Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement date: 2018-07-20 words: 10272.0 sentences: 565.0 pages: flesch: 43.0 cache: ./cache/cord-003122-a3f4l6iu.txt txt: ./txt/cord-003122-a3f4l6iu.txt summary: The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. Influenza A viruses (IAVs) and type B viruses (IBVs) contain 8, negative-sense, single-stranded viral RNA (vRNA) gene segments ( Figure 1A ) (3, 4) , which encode transcripts for 10 essential viral proteins, as well as several strain-dependent accessory proteins ( Figure 1B) . In contrast to the early steps in IAV entry, vRNP trafficking to the nucleus following the fusion event is highly dependent on the host cell machinery and transport pathways [reviewed in Ref. abstract: Influenza viruses replicate within the nucleus of the host cell. This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication. However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection. The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. The aim of this review is to present the current mechanistic understanding for how IAVs facilitate cell entry, replication, virion assembly, and intercellular movement, in an effort to highlight some of the unanswered questions regarding the coordination of the IAV infection process. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062596/ doi: 10.3389/fimmu.2018.01581 id: cord-328003-yovp8squ author: Duan, Liangwei title: The SARS-CoV-2 Spike Glycoprotein Biosynthesis, Structure, Function, and Antigenicity: Implications for the Design of Spike-Based Vaccine Immunogens date: 2020-10-07 words: 7346.0 sentences: 386.0 pages: flesch: 46.0 cache: ./cache/cord-328003-yovp8squ.txt txt: ./txt/cord-328003-yovp8squ.txt summary: Here, we provide a comprehensive overview of the wealth of research related to the SARS-CoV-2 S glycoprotein biosynthesis, structure, function, and antigenicity, aiming to provide useful insights into the design and development of the S protein-based vaccines as well as therapeutics to prevent or treat the ongoing global spread of SARS-CoV-2/COVID-19. Prefusion structures of human coronavirus HKU1 (HCoV-HKU1) and mouse hepatitis virus S protein ectodomains without two consecutive proline mutations reveal only fully closed conformation (37, 42) , similar to that observed for a full-length, wild-type prefusion form of the SARS-CoV-2 S glycoprotein (41) . Therefore, SARS-CoV-2 evades immune surveillance also through conformational masking, which is well-documented for HIV-1 (43, 44) ; while at the same time, the S protein could transiently sample the functional state to engage ACE2, consistent with the notion that the fusion glycoprotein of highly pathogenic viruses have evolved to perform its functions while evading host neutralizing antibody responses. abstract: The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a grave threat to global public health and imposes a severe burden on the entire human society. Like other coronaviruses, the SARS-CoV-2 genome encodes spike (S) glycoproteins, which protrude from the surface of mature virions. The S glycoprotein plays essential roles in virus attachment, fusion and entry into the host cell. Surface location of the S glycoprotein renders it a direct target for host immune responses, making it the main target of neutralizing antibodies. In the light of its crucial roles in viral infection and adaptive immunity, the S protein is the focus of most vaccine strategies as well as therapeutic interventions. In this review, we highlight and describe the recent progress that has been made in the biosynthesis, structure, function, and antigenicity of the SARS-CoV-2 S glycoprotein, aiming to provide valuable insights into the design and development of the S protein-based vaccines as well as therapeutics. url: https://www.ncbi.nlm.nih.gov/pubmed/33117378/ doi: 10.3389/fimmu.2020.576622 id: cord-295416-y3lvcjqd author: Eichinger, Katherine M. title: Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection date: 2020-07-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies with stabilized pre-fusion F protein antigens has been proposed as a strategy to prevent ERD. We sought to test whether there was evidence of ERD in naïve BALB/c mice immunized with an unadjuvanted, stabilized pre-fusion F protein, and challenged with RSV line 19. We further sought to determine the extent to which formulation with a Th2-biased (alum) or a more Th1/Th2-balanced (Advax-SM) adjuvant influenced cellular responses and lung pathology. When exposed to RSV, mice immunized with pre-fusion F protein alone (PreF) exhibited increased airway eosinophilia and mucus accumulation. This was further exacerbated by formulation of PreF with Alum (aluminum hydroxide). Conversely, formulation of PreF with a Th1/Th2-balanced adjuvant, Advax-SM, not only suppressed RSV viral replication, but also inhibited airway eosinophilia and mucus accumulation. This was associated with lower numbers of lung innate lymphocyte cells (ILC2s) and CD4+ T cells producing IL-5+ or IL-13+ and increased IFNγ+ CD4+ and CD8+ T cells, in addition to RSV F-specific CD8+ T cells. These data suggest that in the absence of preimmunity, stabilized PreF antigens may still be associated with aberrant Th2 responses that induce lung pathology in response to RSV infection, and can be prevented by formulation with more Th1/Th2-balanced adjuvants that enhance CD4+ and CD8+ IFNγ+ T cell responses. This may support the use of stabilized PreF antigens with Th1/Th2-balanced adjuvants like, Advax-SM, as safer alternatives to alum in RSV vaccine candidates. url: https://doi.org/10.3389/fimmu.2020.01673 doi: 10.3389/fimmu.2020.01673 id: cord-003598-m2fsrwvw author: Elbahesh, Husni title: Response Modifiers: Tweaking the Immune Response Against Influenza A Virus date: 2019-04-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself. While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections. In addition, antigenic variation of IAV complicates the production of efficacious vaccines. Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs. Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals. Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs). In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response. BRMs are already being used in the clinic to treat malignancies and autoimmune diseases. Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections. In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473099/ doi: 10.3389/fimmu.2019.00809 id: cord-304623-j9ay4jkf author: Entrican, Gary title: The Veterinary Immunological Toolbox: Past, Present, and Future date: 2020-07-28 words: 5541.0 sentences: 252.0 pages: flesch: 33.0 cache: ./cache/cord-304623-j9ay4jkf.txt txt: ./txt/cord-304623-j9ay4jkf.txt summary: We review the past, present and future of the veterinary immunological toolbox with specific reference to recent developments discussed at the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) Immune Toolkit Workshop at the 12th International Veterinary Immunology Symposium (IVIS) in Seattle, USA, 16–19 August 2019. The success of the HLDA workshops was based on good co-ordination, high-quality work and collective effort by the veterinary immunology community, as well as results from past species-specific CD workshops supported by IUIS VIC. A barrier to formal international collaboration was lifted in 2013 when USDA/NIFA and BBSRC launched a pilot call to support animal disease research of strategic importance to both the US and UK which included the development of veterinary immunological reagents for agriculturally-relevant animal species. To date, the concept of the veterinary immunological toolbox has largely (but not exclusively) focused on reagent development for livestock species due to their strategic relevance for funders with a stake in livestock health, food safety and global food security. abstract: It is well-recognized that research capability in veterinary species is restricted by a lack of immunological reagents relative to the extensive toolboxes for small rodent biomedical model species and humans. This creates a barrier to the strategic development of disease control solutions for livestock, companion animals and wildlife that not only affects animal health but can affect human health by increasing the risk of transmission of zoonotic pathogens. There have been a number of projects aimed at reducing the capability gaps in the veterinary immunological toolbox, the majority of these focusing on livestock species. Various approaches have been taken to veterinary immunological reagent development across the globe and technological advances in molecular biology and protein biochemistry have accelerated toolbox development. While short-term funding initiatives can address specific gaps in capability, they do not account for long-term sustainability of reagents and databases that requires a different funding model. We review the past, present and future of the veterinary immunological toolbox with specific reference to recent developments discussed at the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) Immune Toolkit Workshop at the 12th International Veterinary Immunology Symposium (IVIS) in Seattle, USA, 16–19 August 2019. The future availability of these reagents is critical to research for improving animal health, responses to infectious pathogens and vaccine design as well as for important analyses of zoonotic pathogens and the animal /human interface for One Health initiatives. url: https://doi.org/10.3389/fimmu.2020.01651 doi: 10.3389/fimmu.2020.01651 id: cord-354353-hyz0gmpz author: Farhangrazi, Z. Shadi title: Airborne Particulate Matter and SARS-CoV-2 Partnership: Virus Hitchhiking, Stabilization and Immune Cell Targeting — A Hypothesis date: 2020-09-24 words: 2465.0 sentences: 108.0 pages: flesch: 38.0 cache: ./cache/cord-354353-hyz0gmpz.txt txt: ./txt/cord-354353-hyz0gmpz.txt summary: While long-term exposure to air pollutants such as PM 2.5 and nitrous dioxide contributes to persistent inflammatory responses and cardiopulmonary diseases (7) , which might increase vulnerability to COVID-19, it is also plausible that depending on the environment SARS-CoV-2 "hitchhiking" on airborne PM pollutants might be an additional mechanism for spreading the infection. In summary, although long-term exposure to polluted air might increase vulnerability to COVID-19 through prior adverse cellular effects of settled PM (24), our proposed "hitchhiking" hypothesis offers an additional multi-mechanistic pathogenic process through delivery of low viral titres with diverse PM-virus composites and is applicable to both indoor and outdoor situations, where the pathogenic severity is dependent on PM concentration, composition, shape and size as well as the infectious viral load. Contrary to the suggestions that long-term exposure to PM might increase vulnerability to SAR-CoV-2 infection, inhaled PM might promote some forms of immunity to the virus in some individuals. abstract: nan url: https://doi.org/10.3389/fimmu.2020.579352 doi: 10.3389/fimmu.2020.579352 id: cord-338261-tyimwctm author: Farr, Laura title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair date: 2020-06-23 words: 5261.0 sentences: 306.0 pages: flesch: 39.0 cache: ./cache/cord-338261-tyimwctm.txt txt: ./txt/cord-338261-tyimwctm.txt summary: title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair This mini review focuses on emerging literature on the role of the cytokine macrophage migration inhibitory factor (MIF) and its cell membrane receptor CD74, in protecting against injury and promoting healing in different parts of the body. This review focuses on the recent advances that have greatly contributed to our current understanding of the link between the signaling pathways activated upon binding of macrophage migration inhibitory factor cytokine to its membrane receptor CD74 and wound healing in different body parts (Figure 1 ). The complex pathological processes that result in disease combined with CD74''s expression on a variety of cell types, and its multiple co-receptors with diverse downstream signaling pathways contribute to these varied outcomes. Surface expression of CD74 by type II alveolar epithelial cells: a potential mechanism for macrophage migration inhibitory factor-induced epithelial repair abstract: Wound healing after an injury is essential for life. An in-depth understanding of the healing process is necessary to ultimately improve the currently limited treatment options for patients suffering as a result of damage to various organs and tissues. Injuries, even the most minor, trigger an inflammatory response that protects the host and activates repair pathways. In recent years, substantial progress has been made in delineating the mechanisms by which inflammatory cytokines and their receptors facilitate tissue repair and regeneration. This mini review focuses on emerging literature on the role of the cytokine macrophage migration inhibitory factor (MIF) and its cell membrane receptor CD74, in protecting against injury and promoting healing in different parts of the body. url: https://www.ncbi.nlm.nih.gov/pubmed/32655566/ doi: 10.3389/fimmu.2020.01273 id: cord-264814-v4wnmg03 author: Flanagan, Katie L. title: Progress and Pitfalls in the Quest for Effective SARS-CoV-2 (COVID-19) Vaccines date: 2020-10-02 words: 15130.0 sentences: 700.0 pages: flesch: 44.0 cache: ./cache/cord-264814-v4wnmg03.txt txt: ./txt/cord-264814-v4wnmg03.txt summary: Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. Comprehensive safety studies are particularly critical because some candidate vaccines use platform technologies that have not been examined extensively in human subjects to date, including some of the viral vectors, mRNA and nanoparticle constructs, and because of the potential for enhanced disease and adverse events related to aberrant immune responses to be seen upon infection pre-and post-licensure. abstract: There are currently around 200 SARS-CoV-2 candidate vaccines in preclinical and clinical trials throughout the world. The various candidates employ a range of vaccine strategies including some novel approaches. Currently, the goal is to prove that they are safe and immunogenic in humans (phase 1/2 studies) with several now advancing into phase 2 and 3 trials to demonstrate efficacy and gather comprehensive data on safety. It is highly likely that many vaccines will be shown to stimulate antibody and T cell responses in healthy individuals and have an acceptable safety profile, but the key will be to confirm that they protect against COVID-19. There is much hope that SARS-CoV-2 vaccines will be rolled out to the entire world to contain the pandemic and avert its most damaging impacts. However, in all likelihood this will initially require a targeted approach toward key vulnerable groups. Collaborative efforts are underway to ensure manufacturing can occur at the unprecedented scale and speed required to immunize billions of people. Ensuring deployment also occurs equitably across the globe will be critical. Careful evaluation and ongoing surveillance for safety will be required to address theoretical concerns regarding immune enhancement seen in previous contexts. Herein, we review the current knowledge about the immune response to this novel virus as it pertains to the design of effective and safe SARS-CoV-2 vaccines and the range of novel and established approaches to vaccine development being taken. We provide details of some of the frontrunner vaccines and discuss potential issues including adverse effects, scale-up and delivery. url: https://doi.org/10.3389/fimmu.2020.579250 doi: 10.3389/fimmu.2020.579250 id: cord-282081-qaagup4d author: Flicker, Sabine title: Nanobodies—Useful Tools for Allergy Treatment? date: 2020-09-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: In the last decade single domain antibodies (nanobodies, V(H)H) qualified through their unique characteristics have emerged as accepted and even advantageous alternative to conventional antibodies and have shown great potential as diagnostic and therapeutic tools. Currently nanobodies find their main medical application area in the fields of oncology and neurodegenerative diseases. According to late-breaking information, nanobodies specific for coronavirus spikes have been generated these days to test their suitability as useful therapeutics for future outbreaks. Their superior properties such as chemical stability, high affinity to a broad spectrum of epitopes, low immunogenicity, ease of their generation, selection and production proved nanobodies also to be remarkable to investigate their efficacy for passive treatment of type I allergy, an exaggerated immune reaction to foreign antigens with increasing global prevalence. url: https://doi.org/10.3389/fimmu.2020.576255 doi: 10.3389/fimmu.2020.576255 id: cord-305936-tdswzj7r author: Freitas, André Ricardo Ribas title: Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil date: 2018-01-08 words: 4343.0 sentences: 193.0 pages: flesch: 39.0 cache: ./cache/cord-305936-tdswzj7r.txt txt: ./txt/cord-305936-tdswzj7r.txt summary: Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. We analyzed particularly the most predominant variants (AH1N1 and AH3N2) on excess of mortality in the adults and elderly of different age groups in a region with marked seasonality of respiratory diseases in Brazil. Among adults (24-59 years), we observe a large excess of deaths rates during the 2009 pandemic (953 obits), which correspond to 7.1 excess deaths from all causes, and 99 excess mortality from respiratory diseases associated with viral infection in every 100,000 individuals of the age group. Although the elderly are the most vulnerable group to viral respiratory infections, we found relative small excess of deaths in years of circulating AH1N1 pre pandemic (2002 and 2008) . abstract: PURPOSE: In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with different predominant virus strains. METHODS: We performed a time trend study to evaluated excess of mortality for pneumonia and influenza, respiratory disease, and all-causes in southern region of Brazil, from 2002 to 2015. After considering other models, we opted for Serfling regression. Excess of death rates per 100,000 inhabitants were analyzed in specific age groups (24–59, 60–69, 70–79, ≥80 years) and by year of occurrence. Mortality information were taken from Brazilian Mortality Information System and etiological data were accessed in Sentinel Virological Surveillance database, getting the weekly positivity of the immunofluorescence tests for influenza A (H1N1, H3N2), and B. RESULTS: In southern Brazil, there is an evident seasonal pattern of all death outcomes among different age groups in the dry and cold season (April–September). The highest excess mortality rates occurs among older, particularly in years of circulation of influenza AH3N2, especially among people ≥80 years, in 2003 and 2007—years of great severity of influenza activity. After 2009, with the introduction of the pandemic influenza AH1N1, we observed a lower impact on the mortality of the elderly compared to <60 years. DISCUSSION: A cross reactivity antibody response from past exposure probably provided protection against disease in the elderly. Despite not controlling for comorbidities, climate, and vaccination, for the >70 years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009) and severe year of H3N2 (2007) shows protection in the pandemic year and great vulnerability during AH3N2 virus predominance. CONCLUSION: The reduced immune response to infection, and to vaccination, and presence of comorbidities recommend a special attention to this age group in Brazil. Besides medical assistance, the timeliness of vaccine campaigns, its composition, and etiological surveillance of respiratory diseases are some of the preventive and public health measures. url: https://doi.org/10.3389/fimmu.2017.01903 doi: 10.3389/fimmu.2017.01903 id: cord-320431-0877trhh author: Frey, Andreas title: More Than Just a Barrier: The Immune Functions of the Airway Epithelium in Asthma Pathogenesis date: 2020-04-28 words: 15225.0 sentences: 762.0 pages: flesch: 40.0 cache: ./cache/cord-320431-0877trhh.txt txt: ./txt/cord-320431-0877trhh.txt summary: In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Besides this innate "rapid response team, " the polarized epithelium of the human airways is also able to transport and apically release immunoglobulins that carry a J-chain (joining chain) by using its poly Ig receptor (pIgR) (145) (146) (147) that is expressed by all non-stratified epithelial cells (Figure 2) . After contact for example with HDM extracts, representing a major source of asthma associated allergens, TLR4 dependent activation of NFκB and protease induced injuries in airway epithelial cells lead to secretion of chemokines and cytokines like thymic stromal lymphopoietin (TSLP), GM-CSF, IL-25, and IL-33 (211) (212) (213) (214) (215) . abstract: Allergic bronchial asthma is a chronic disease of the airways that is characterized by symptoms like respiratory distress, chest tightness, wheezing, productive cough, and acute episodes of broncho-obstruction. This symptom-complex arises on the basis of chronic allergic inflammation of the airway wall. Consequently, the airway epithelium is central to the pathogenesis of this disease, because its multiple abilities directly have an impact on the inflammatory response and thus the formation of the disease. In turn, its structure and functions are markedly impaired by the inflammation. Hence, the airway epithelium represents a sealed, self-cleaning barrier, that prohibits penetration of inhaled allergens, pathogens, and other noxious agents into the body. This barrier is covered with mucus that further contains antimicrobial peptides and antibodies that are either produced or specifically transported by the airway epithelium in order to trap these particles and to remove them from the body by a process called mucociliary clearance. Once this first line of defense of the lung is overcome, airway epithelial cells are the first cells to get in contact with pathogens, to be damaged or infected. Therefore, these cells release a plethora of chemokines and cytokines that not only induce an acute inflammatory reaction but also have an impact on the alignment of the following immune reaction. In case of asthma, all these functions are impaired by the already existing allergic immune response that per se weakens the barrier integrity and self-cleaning abilities of the airway epithelium making it more vulnerable to penetration of allergens as well as of infection by bacteria and viruses. Recent studies indicate that the history of allergy- and pathogen-derived insults can leave some kind of memory in these cells that can be described as imprinting or trained immunity. Thus, the airway epithelium is in the center of processes that lead to formation, progression and acute exacerbation of asthma. url: https://doi.org/10.3389/fimmu.2020.00761 doi: 10.3389/fimmu.2020.00761 id: cord-353594-z1vxamvp author: Gagiannis, Daniel title: Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) date: 2020-10-02 words: 4997.0 sentences: 246.0 pages: flesch: 40.0 cache: ./cache/cord-353594-z1vxamvp.txt txt: ./txt/cord-353594-z1vxamvp.txt summary: Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. Patients or their relatives had given written informed consent to routine diagnostic procedures (serology, bronchoscopy, radiology) as well as (partial) autopsy in the case of death, respectively, as well as to the scientific use of data and tissue samples in the present study. Our finding that significant ANA titers and/or detection of specific autoantibodies are found in most patients who develop ARDS raises the question if there is a comparable mechanism of lung damage between SARS-CoV-2 infection and exacerbating autoimmune disease. Our observation of CTD-associated autoantibodies together with the CTD-like radiologic and histopathologic lung findings in severe cases of COVID-19 point towards a possible dysregulation of the immune response upon SARS-CoV-2 infection that might fuel organizing pneumonia and trigger interstitial fibrosis, with deleterious effects on the functional outcome in long-term survivors. abstract: BACKGROUND AND OBJECTIVES: Understanding the pathophysiology of respiratory failure in coronavirus disease 2019 (COVID-19) is indispensable for development of therapeutic strategies. Since we observed similarities between COVID-19 and interstitial lung disease in connective tissue disease (CTD-ILD), we investigated features of autoimmunity in SARS-CoV-2-associated respiratory failure. METHODS: We prospectively enrolled 22 patients with RT-PCR-confirmed SARS-CoV-2 infection and 10 patients with non-COVID-19-associated pneumonia. Full laboratory testing was performed including autoantibody (AAB; ANA/ENA) screening using indirect immunofluorescence and immunoblot. Fifteen COVID-19 patients underwent high-resolution computed tomography. Transbronchial biopsies/autopsy tissue samples for histopathology and ultrastructural analyses were obtained from 4/3 cases, respectively. RESULTS: Thirteen (59.1%) patients developed acute respiratory distress syndrome (ARDS), and five patients (22.7%) died from the disease. ANA titers ≥1:320 and/or positive ENA immunoblots were detected in 11/13 (84.6%) COVID-19 patients with ARDS, in 1/9 (11.1%) COVID-19 patients without ARDS (p = 0.002) and in 4/10 (40%) patients with non-COVID-19-associated pneumonias (p = 0.039). Detection of AABs was significantly associated with a need for intensive care treatment (83.3 vs. 10%; p = 0.002) and occurrence of severe complications (75 vs. 20%, p = 0.03). Radiological and histopathological findings were highly heterogeneous including patterns reminiscent of exacerbating CTD-ILD, while ultrastructural analyses revealed interstitial thickening, fibroblast activation, and deposition of collagen fibrils. CONCLUSIONS: We are the first to report overlapping clinical, serological, and imaging features between severe COVID-19 and acute exacerbation of CTD-ILD. Our findings indicate that autoimmune mechanisms determine both clinical course and long-term sequelae after SARS-CoV-2 infection, and the presence of autoantibodies might predict adverse clinical course in COVID-19 patients. url: https://doi.org/10.3389/fimmu.2020.587517 doi: 10.3389/fimmu.2020.587517 id: cord-313117-0qur0isb author: Gardinassi, Luiz G. title: Immune and Metabolic Signatures of COVID-19 Revealed by Transcriptomics Data Reuse date: 2020-06-26 words: 3565.0 sentences: 177.0 pages: flesch: 35.0 cache: ./cache/cord-313117-0qur0isb.txt txt: ./txt/cord-313117-0qur0isb.txt summary: To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. In addition, our approach also detected increased signals of monocytes (Figure 1B) , dendritic cells ( Figure 1C ) and of the mitochondrial respiratory electron transport chain in SARS-CoV-2 infection (Figure 1A) , suggesting a critical role of metabolic pathways for the immune response of COVID-19 patients. abstract: The current pandemic of coronavirus disease 19 (COVID-19) has affected millions of individuals and caused thousands of deaths worldwide. The pathophysiology of the disease is complex and mostly unknown. Therefore, identifying the molecular mechanisms that promote progression of the disease is critical to overcome this pandemic. To address such issues, recent studies have reported transcriptomic profiles of cells, tissues and fluids from COVID-19 patients that mainly demonstrated activation of humoral immunity, dysregulated type I and III interferon expression, intense innate immune responses and inflammatory signaling. Here, we provide novel perspectives on the pathophysiology of COVID-19 using robust functional approaches to analyze public transcriptome datasets. In addition, we compared the transcriptional signature of COVID-19 patients with individuals infected with SARS-CoV-1 and Influenza A (IAV) viruses. We identified a core transcriptional signature induced by the respiratory viruses in peripheral leukocytes, whereas the absence of significant type I interferon/antiviral responses characterized SARS-CoV-2 infection. We also identified the higher expression of genes involved in metabolic pathways including heme biosynthesis, oxidative phosphorylation and tryptophan metabolism. A BTM-driven meta-analysis of bronchoalveolar lavage fluid (BALF) from COVID-19 patients showed significant enrichment for neutrophils and chemokines, which were also significant in data from lung tissue of one deceased COVID-19 patient. Importantly, our results indicate higher expression of genes related to oxidative phosphorylation both in peripheral mononuclear leukocytes and BALF, suggesting a critical role for mitochondrial activity during SARS-CoV-2 infection. Collectively, these data point for immunopathological features and targets that can be therapeutically exploited to control COVID-19. url: https://doi.org/10.3389/fimmu.2020.01636 doi: 10.3389/fimmu.2020.01636 id: cord-338092-barmkkwx author: Geginat, Jens title: Immunity to Pathogens Taught by Specialized Human Dendritic Cell Subsets date: 2015-10-13 words: 8573.0 sentences: 421.0 pages: flesch: 45.0 cache: ./cache/cord-338092-barmkkwx.txt txt: ./txt/cord-338092-barmkkwx.txt summary: Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. BDCA-3(+) mDC2 are the human homologue of CD8α(+) mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8(+) T-cells and to produce IFN-λ. Dendritic cells (DCs) can express very high levels of MHC and costimulatory molecules, and it is generally accepted that they are the relevant cells to induce the activation ("priming") of antigen-specific "naive" T cells (1, 2) and induce their differentiation into various types of effector T cells. Overall, these differences in pathogen sensing and T-cell activation between human and murine DCs are likely to have an important impact on their role in immune responses against specific pathogens. Dendritic cell subsets in humans and mice express not only different patterns of toll-like receptors, but they have also partially distinct cytokine profiles (Figure 1) . abstract: Dendritic cells (DCs) are specialized antigen-presenting cells (APCs) that have a key role in immune responses because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and upregulate MHC molecules and costimulatory receptors to activate antigen-specific CD4(+) and CD8(+) T cells. It is now well established that DCs are not a homogeneous population but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DCs (pDCs) rapidly produce large amounts of IFN-α, which has potent antiviral functions and activates several other immune cells. However, pDCs are not particularly potent APCs and induce the tolerogenic cytokine IL-10 in CD4(+) T cells. In contrast, myeloid DCs (mDCs) are very potent APCs and possess the unique capacity to prime naive T cells and consequently to initiate a primary adaptive immune response. Different subsets of mDCs with specialized functions have been identified. In mice, CD8α(+) mDCs capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T-cell responses to control intracellular pathogens. Conversely, CD8α(−) mDCs preferentially prime CD4(+) T cells and promote Th2 or Th17 differentiation. BDCA-3(+) mDC2 are the human homologue of CD8α(+) mDCs, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8(+) T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggest specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the development of vaccines against persistent infections or cancer. url: https://doi.org/10.3389/fimmu.2015.00527 doi: 10.3389/fimmu.2015.00527 id: cord-003685-jcvrqeew author: Gelain, Maria Elena title: Acute Phase Proteins in Marine Mammals: State of Art, Perspectives and Challenges date: 2019-05-29 words: 4630.0 sentences: 207.0 pages: flesch: 37.0 cache: ./cache/cord-003685-jcvrqeew.txt txt: ./txt/cord-003685-jcvrqeew.txt summary: The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp). To examine the humoral response, species-specific antibodies against IgG were produced and used to evaluate serum IgG levels in killer whale by radial immunodiffusion assay (41) and by competitive ELISA in bottlenose dolphins (42, 43) . Serum total protein analysis were used to assess health status in several cetaceans species such as pantropical spotted dolphins (Stenella attenuata) (48), beluga (49) , minke whales (Balaenoptera acutorostrata) (50) and killer whales (51) as well as in other marine mammals, like harbor seals (Phoca vitulina) (52) and walruses (Odobenus rosmarus) (53) . The availability of sensitive markers of inflammation both for free-ranging and managed marine mammals is nowadays considered fundamental to evaluate the health status and, in rehabilitation setting, to monitor the response to therapy and to define the prognosis. abstract: The term “acute phase response” (APR) is referred to a nonspecific and complex reaction of an organism that occurs shortly after any tissue damage, such as infection, trauma, neoplasia, inflammation, and stress. The APR can be identified and monitored with some laboratory tests, such as the concentration of several plasma proteins, the acute phase proteins (APPs). The APPs are components of the non-specific innate immune response, and their plasma concentration is proportional to the severity and/or the extent of tissue damage. The evaluation of health status of marine mammals is difficult because the classical clinical signs of illness used for human and domestic animals are difficult to recognize and understand. For this reason, in the past years, several efforts were done to identify laboratory markers of disease in these animals. The APPs have demonstrated their role as early markers of inflammation in veterinary medicine, thus several APPs were tested in marine mammals, such as C-reactive protein (CRP), serum amyloid-A (SAA), and Haptoglobin (Hp). However, the difficulty to extrapolate the knowledge about APPs in one species to another, the lack of specie-specific reagents, the absence of data about negative APPs have hampered their extent use in marine mammals. Herein, the state of art of APPs in marine mammals is reviewed, with particular attention to pre-analytical and analytical factors that should be taken into account in validation and interpretation of APPs assays. Moreover, the current application, potential utility and the future developments of APPs in marine mammals is highlighted and discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549532/ doi: 10.3389/fimmu.2019.01220 id: cord-003091-uvfppirt author: Gornati, Laura title: Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines date: 2018-06-27 words: 9424.0 sentences: 460.0 pages: flesch: 40.0 cache: ./cache/cord-003091-uvfppirt.txt txt: ./txt/cord-003091-uvfppirt.txt summary: Taking advantage of new adjuvants, innovative ags-delivery carriers and targeting strategies, it is now feasible to optimize the activation and ag presentation processes by the specific DCs subset that is the most effective in the initiation of the adaptive response needed in a given context. Indeed, MF59, an oil-in-water emulsion adjuvant, that allows long-lasting ag retention in draining LN and enhanced ag uptake by LN-resident DCs, promotes robust humoral responses via follicular DC activation (43) and CD4 + T cell immunity induction (44) . In addition to the use of NPs, targeting DC-specific receptors has become an attractive strategy for vaccine development due to the enforced efficiency of immune responses when compared to generic-delivering approaches. Moreover, vaccines based on the filamentous bacteriophage fd presenting an αDEC-205 scFv, efficiently induce DCs maturation via the activation of the TLR9-MyD88 pathway (144) , without adjuvants and further elicit potent antitumor responses when compared to non-tailored ag delivery (145) . abstract: Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030256/ doi: 10.3389/fimmu.2018.01484 id: cord-267237-wbwlfx7q author: Gómez-Rial, Jose title: Increased Serum Levels of sCD14 and sCD163 Indicate a Preponderant Role for Monocytes in COVID-19 Immunopathology date: 2020-09-23 words: 2589.0 sentences: 148.0 pages: flesch: 40.0 cache: ./cache/cord-267237-wbwlfx7q.txt txt: ./txt/cord-267237-wbwlfx7q.txt summary: METHODS: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. CONCLUSIONS: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. In this paper, we analyze serum levels of soluble monocyte activation markers in COVID-19 patients and their correlation with severity and other inflammatory markers. We found significant correlations between sCD14 and sCD163 levels and several clinical laboratory parameters in infected patients (in these analysis, adjusted significance under Bonferrori correction is 0.01), but only in the non-ICU group, possibly reflecting an interference of the use of tocilizumab or corticoids in the ICU group. Our results thus suggest that monocyte-macrophage activation can act as driver cells of the cytokine storm and immunopathology associated to severe clinical course of COVID-19 patients. abstract: BACKGROUND: Emerging evidence indicates a potential role for monocytes in COVID-19 immunopathology. We investigated two soluble markers of monocyte activation, sCD14 and sCD163, in COVID-19 patients, with the aim of characterizing their potential role in monocyte-macrophage disease immunopathology. To the best of our knowledge, this is the first study of its kind. METHODS: Fifty-nine SARS-Cov-2 positive hospitalized patients, classified according to ICU or non-ICU admission requirement, were prospectively recruited and analyzed by ELISA for levels of sCD14 and sCD163, along with other laboratory parameters, and compared to a healthy control group. RESULTS: sCD14 and sCD163 levels were significantly higher among COVID-19 patients, independently of ICU admission requirement, compared to the control group. We found a significant correlation between sCD14 levels and other inflammatory markers, particularly Interleukin-6, in the non-ICU patients group. sCD163 showed a moderate positive correlation with the time lapsed from admission to sampling, independently of severity group. Treatment with corticoids showed an interference with sCD14 levels, whereas hydroxychloroquine and tocilizumab did not. CONCLUSIONS: Monocyte-macrophage activation markers are increased and correlate with other inflammatory markers in SARS-Cov-2 infection, in association to hospital admission. These data suggest a preponderant role for monocyte-macrophage activation in the development of immunopathology of COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/33072099/ doi: 10.3389/fimmu.2020.560381 id: cord-352960-pfccsgco author: Gössling, Katharina L. title: Hematopoietic Stem Cell Transplantation in an Infant with Immunodeficiency, Centromeric Instability, and Facial Anomaly Syndrome date: 2017-06-30 words: 3292.0 sentences: 176.0 pages: flesch: 43.0 cache: ./cache/cord-352960-pfccsgco.txt txt: ./txt/cord-352960-pfccsgco.txt summary: Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. Here, we report the case of a 1-year-old boy of Moroccan consanguineous descent diagnosed with ICF syndrome carrying a homozygous missense mutation in the DNMT3B gene (Ala603Thr) with hypogammagobulinemia, normal B cell count, facial anomaly, and failure to thrive. We report the successful allogeneic HSCT of a 1-year-old boy with ICF1 syndrome carrying a homozygous mutation in the DNMT3B gene after receipt of bone marrow cells from the 10/10 HLA-matched clinically healthy sister. abstract: Immunodeficiency, centromeric instability, and facial anomaly (ICF) syndrome is a rare autosomal recessive genetic condition with severe immunodeficiency, which leads to lethal infections if not recognized and treated in early childhood. Up-to-date treatment regimens consist of prophylactic and supportive treatment of the recurrent infections. Here, we report the case of a 1-year-old boy of Moroccan consanguineous parents, who was diagnosed at 4 months of age with ICF syndrome with a homozygous missense mutation in the DNMT3B gene. He was initially admitted to the hospital with recurrent pulmonary infections from the opportunistic pathogen Pneumocystis jirovecii (PJ). Further immunological workup revealed agammaglobulinemia in the presence of B cells. After successful recovery from the PJ pneumonia, he underwent hematopoietic stem cell transplantation (HSCT) from the HLA-matched healthy sister using a chemotherapeutic conditioning regimen consisting of treosulfan, fludarabine, and thiotepa. Other than acute chemotherapy-associated side effects, no serious adverse events occurred. Six months after HSCT immune-reconstitution, he had a stable chimerism with 2.9% autologous portion in the peripheral blood and a normal differential blood cell count, including all immunoglobulin subtypes. This is one of the first cases of successful HSCT in ICF syndrome. Early diagnosis and subsequent HSCT can prevent severe opportunistic infections and cure the immunodeficiency. Centromeric instability and facial anomaly remain unaffected. Although the long-term patient outcome and the neurological development remain to be seen, this curative therapy for immunodeficiency improves life expectancy and quality of life. This case is meant to raise physicians awareness for ICF syndrome and highlight the consideration for HSCT in ICF syndrome early on. url: https://doi.org/10.3389/fimmu.2017.00773 doi: 10.3389/fimmu.2017.00773 id: cord-280924-g6062fwk author: Hachim, Mahmood Yaseen title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells date: 2020-06-10 words: 2851.0 sentences: 147.0 pages: flesch: 42.0 cache: ./cache/cord-280924-g6062fwk.txt txt: ./txt/cord-280924-g6062fwk.txt summary: title: Interferon-Induced Transmembrane Protein (IFITM3) Is Upregulated Explicitly in SARS-CoV-2 Infected Lung Epithelial Cells We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. To effectively address the ongoing COVID-19 pandemic, there is a recognized need for a framework for rapid identification of novel targets for diagnostic and therapeutic interventions as well as determine clinically approved drugs with high potential for repurposed use against SARS-CoV-2. In this study, we have applied this approach, and our findings have identified IFITM3 as an early upregulated gene and indicate that valproic acid enhances IFITM3 mRNA expression and antiviral action. Our toxicogenomic analysis showed that valproic acid increased the mRNA expression of IFITM3, supporting a new report that the SARS-CoV-2-human protein-protein interaction map showed that valproic acid might be a potential repurposing drug for COVID-19 (34) . abstract: Current guidelines for COVID-19 management recommend the utilization of various repurposed drugs. Despite ongoing research toward the development of a vaccine against SARS-CoV-2, such a vaccine will not be available in time to contribute to the containment of the ongoing pandemic. Therefore, there is an urgent need to develop a framework for the rapid identification of novel targets for diagnostic and therapeutic interventions. We analyzed publicly available transcriptomic datasets of SARS-CoV infected humans and mammals to identify consistent differentially expressed genes then validated in SARS-CoV-2 infected epithelial cells transcriptomic datasets. Comprehensive toxicogenomic analysis of the identified genes to identify possible interactions with clinically proven drugs was carried out. We identified IFITM3 as an early upregulated gene, and valproic acid was found to enhance its mRNA expression as well as induce its antiviral action. These findings indicate that analysis of publicly available transcriptomic and toxicogenomic data represents a rapid approach for the identification of novel targets and molecules that can modify the action of such targets during the early phases of emerging infections like COVID-19. url: https://doi.org/10.3389/fimmu.2020.01372 doi: 10.3389/fimmu.2020.01372 id: cord-286337-qk90xb3a author: Hanada, Shigeo title: Respiratory Viral Infection-Induced Microbiome Alterations and Secondary Bacterial Pneumonia date: 2018-11-16 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza and other respiratory viral infections are the most common type of acute respiratory infection. Viral infections predispose patients to secondary bacterial infections, which often have a more severe clinical course. The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system. Studies over the past 15 years have demonstrated that unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract, which have both direct and indirect effects on host defense against viral infections. In addition, antiviral immune responses induced by acute respiratory infections such as influenza are associated with changes in microbial composition and function (“dysbiosis”) in the respiratory and gastrointestinal tract, which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species. In this review, we summarize the literature on the interactions between host microbial communities and host defense, and how influenza, and other acute respiratory viral infections disrupt these interactions, thereby contributing to the pathogenesis of secondary bacterial infections. url: https://doi.org/10.3389/fimmu.2018.02640 doi: 10.3389/fimmu.2018.02640 id: cord-254809-o454k6ae author: He, Bing title: The Metabolic Changes and Immune Profiles in Patients With COVID-19 date: 2020-08-28 words: 4761.0 sentences: 276.0 pages: flesch: 60.0 cache: ./cache/cord-254809-o454k6ae.txt txt: ./txt/cord-254809-o454k6ae.txt summary: Third, according to an analysis of nearly 45,000 confirmed cases, 19% of patients with COVID-19 have been identified as severe cases and critically ill cases, involving severe pneumonia and metabolic disorders, developing into acute respiratory distress syndrome (ARDS), multiple organ dysfunctions (MODS), and even septic shock and death (9, 12) . In this study, we investigated mild cases and severe cases infected with SARS-CoV-2, as well as healthy young children and adults. Our study suggests that monocytes, neutrophils, and T-lymphocytes are associated with the onset and progress of COVID-19 infection, and immunopathogenesis was involved in ARDS, metabolic disorders, and MODS in severe cases. We collected the data of patients with COVID-19, including the clinical records, laboratory results and chest computed tomography (CT) scan images of mild and severe cases in the hospital. Extremely high levels of circulating lymphocytes and monocytes would benefit to fight against SARS-CoV-2 infection, which might be associated with the low morbidity of COVID-19 in young children. abstract: To explore the metabolic changes and immune profiles in patients with COVID-19, we analyzed the data of patients with mild and severe COVID-19 as well as young children with COVID-19. Of the leukocytes, 47% (IQR, 33–59) were lymphocytes [2.5 × 10(9)/L (IQR, 2.2–3.3)], and monocytes were 0.51 × 10(9)/L (IQR, 0.45–0.57) in young children with COVID-19. In 32 mild COVID-19 patients, circulating monocytes were 0.45 × 10(9)/L (IQR, 0.36–0.64). Twenty-one severe patients had low PO(2) [57 mmHg (IQR, 50–73)] and SO(2) [90% (IQR, 86–93)] and high lactate dehydrogenase [580 U/L (IQR, 447–696)], cardiac troponin I [0.07 ng/mL (IQR, 0.02–0.30)], and pro-BNP [498 pg/mL (IQR, 241–1,726)]. Serum D-dimer and FDP were 9.89 mg/L (IQR, 3.62–22.85) and 32.7 mg/L (IQR, 12.8–81.9), and a large number of RBC (46/μL (IQR, 4–242) was presented in urine, a cue of disseminated intravascular coagulation (DIC) in severe patients. Three patients had comorbidity with diabetes, and 18 patients without diabetes also presented high blood glucose [7.4 mmol/L (IQR, 5.9–10.1)]. Fifteen of 21 (71%) severe cases had urine glucose +, and nine of 21 (43%) had urine ketone body +. The increased glucose was partially caused by reduced glucose consumption of cells. Severe cases had extraordinarily low serum uric acid [176 μmol/L (IQR, 131–256)]. In the late stage of COVID-19, severe cases had extremely low CD4(+) T cells and CD8(+) T cells, but unusually high neutrophils [6.5 × 10(9)/L (IQR, 4.8–9.6)], procalcitonin [0.27 ng/mL (IQR, 0.14–1.94)], C-reactive protein [66 mg/L (IQR, 25–114)] and an extremely high level of interleukin-6. Four of 21 (19%) severe cases had co-infection with fungi, and two of 21 (9%) severe cases had bacterial infection. Our findings suggest that, severe cases had acute respiratory distress syndrome (ARDS) I–III, and metabolic disorders of glucose, lipid, uric acid, etc., even multiple organ dysfunction (MODS) and DIC. Increased neutrophils and severe inflammatory responses were involved in ARDS, MODS, and DIC. With the dramatical decrease of T-lymphocytes, severe cases were susceptible to co-infect with bacteria and fungi in the late stage of COVID-19. In young children, extremely high lymphocytes and monocytes might be associated with the low morbidity of COVID-19. The significantly increased monocytes might play an important role in the recovery of patients with mild COVID-19. url: https://doi.org/10.3389/fimmu.2020.02075 doi: 10.3389/fimmu.2020.02075 id: cord-330417-8nnobx8g author: Herrmann, Marissa title: Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease date: 2020-08-26 words: 8853.0 sentences: 399.0 pages: flesch: 51.0 cache: ./cache/cord-330417-8nnobx8g.txt txt: ./txt/cord-330417-8nnobx8g.txt summary: Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8 + and CD4 + T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8 + and CD4 + T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. abstract: Coronavirus disease 2019 (COVID-19) which is caused by the novel SARS-CoV-2 virus is a severe flu-like illness which is associated with hyperinflammation and immune dysfunction. The virus induces a strong T and B cell response but little is known about the immune pathology of this viral infection. Acute Plasmodium falciparum malaria also causes acute clinical illness and is characterized by hyperinflammation due to the strong production of pro-inflammatory cytokines and a massive activation of T cells. In malaria, T cells express a variety of co-inhibitory receptors which might be a consequence of their activation but also might limit their overwhelming function. Thus, T cells are implicated in protection as well as in pathology. The outcome of malaria is thought to be a consequence of the balance between co-activation and co-inhibition of T cells. Following the hypothesis that T cells in COVID-19 might have a similar, dual function, we comprehensively characterized the differentiation (CCR7, CD45RO) and activation status (HLA-DR, CD38, CD69, CD226), the co-expression of co-inhibitory molecules (PD1, TIM-3, LAG-3, BTLA, TIGIT), as well as the expression pattern of the transcription factors T-bet and eomes of CD8(+) and CD4(+) T cells of PBMC of n = 20 SARS-CoV-2 patients compared to n = 10 P. falciparum infected patients and n = 13 healthy controls. Overall, acute COVID-19 and malaria infection resulted in a comparably elevated activation and altered differentiation status of the CD8(+) and CD4(+) T cell populations. T effector cells of COVID-19 and malaria patients showed higher frequencies of the inhibitory receptors T-cell immunoglobulin mucin-3 (TIM-3) and Lymphocyte-activation gene-3 (LAG-3) which was linked to increased activation levels and an upregulation of the transcription factors T-bet and eomes. COVID-19 patients with a more severe disease course showed higher levels of LAG-3 and TIM-3 than patients with a mild disease course. During recovery, a rapid normalization of these inhibitory receptors could be observed. In summary, comparing the expression of different co-inhibitory molecules in CD8(+) and CD4(+) T cells in COVID-19 vs. malaria, there is a transient increase of the expression of certain inhibitory receptors like LAG-3 and TIM-3 in COVID-19 in the overall context of acute immune activation. url: https://www.ncbi.nlm.nih.gov/pubmed/32983106/ doi: 10.3389/fimmu.2020.01870 id: cord-033488-du8heorx author: Ho, Thuong Thi title: Plant-Derived Trimeric CO-26K-Equivalent Epitope Induced Neutralizing Antibodies Against Porcine Epidemic Diarrhea Virus date: 2020-09-16 words: 5435.0 sentences: 267.0 pages: flesch: 47.0 cache: ./cache/cord-033488-du8heorx.txt txt: ./txt/cord-033488-du8heorx.txt summary: (A) Sera from five mice from each group immunized with a negative control (wild-type crude extract, G1) or a positive control (commercial vaccine, G2) or the crude extract containing COE-GCN4pII (G3) were mixed, diluted 200 times and used as a primary antibody for detecting 1 µg of purified PEDV antigen. Different levels of PEDV-specific IgG (B), IgA (C), and IgM (D) antibodies in each mouse sera group were calculated as the reciprocal of the geometric mean titer of the five mice of each group vaccinated with the negative control (wild-type crude extract, G1) or the positive control (commercial vaccine, G2) or the crude extract containing COE-GCN4pII (G3). Therefore, plant crude extract containing the trimeric COE protein had the level of IgG antibodies similar to that of commercial vaccines against the PEDV DR13 strain after the third injection. Therefore, we concluded that plant crude extract containing the trimeric COE protein had a strong immunogenicity and induced a neutralizing antibody titer similar to that of the commercial vaccine against the attenuated PEDV DR13 strain. abstract: Porcine epidemic diarrhea virus (PEDV) is a causative agent of a highly infectious disease with a high mortality rate, especially in newborn piglets in Asian countries resulting in serious economic loss. The development of a rapid, safe, effective and cost-efficient vaccine is crucial to protect pigs against PEDV infection. The COE antigen is regarded to be a major target for subunit vaccine development against PEDV infection. The naturally assembled COE protein forms a homotrimeric structure. In the present study, we successfully produced a trimeric COE protein as a native structure by fusion with the C-terminal isoleucine zipper trimerization (GCN4pII) motif in Nicotiana benthamiana, with a high expression level shown via semi-quantified Western blots. Trimeric COE protein was purified via immobilized metal affinity chromatography (IMAC), and its trimeric structure was successfully demonstrated by a cross-linking reaction, and a native PAGE gel. A crude extract containing the COE trimer was used for evaluating immunogenicity in mice. After 1 and 2 booster immunizations, the crude extract containing trimeric COE elicited elevated PEDV-specific humoral responses, as demonstrated by ELISA and Western blot analyses. Notably, a virus-neutralizing antibody assay indicated that the neutralization activities of sera of mice vaccinated with the crude extract containing COE-GCN4pII were similar to those of mice vaccinated with a commercial vaccine. These results suggest that crude extract containing trimeric COE is a promising plant-based subunit vaccine candidate for PEDV prevention. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524870/ doi: 10.3389/fimmu.2020.02152 id: cord-312438-zr9zx7pv author: Hoo, Regina title: Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface date: 2020-09-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations. url: https://doi.org/10.3389/fimmu.2020.02070 doi: 10.3389/fimmu.2020.02070 id: cord-283505-ousbar6c author: Horman, William S. J. title: The Dynamics of the Ferret Immune Response During H7N9 Influenza Virus Infection date: 2020-09-24 words: 5896.0 sentences: 266.0 pages: flesch: 45.0 cache: ./cache/cord-283505-ousbar6c.txt txt: ./txt/cord-283505-ousbar6c.txt summary: To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. In this study, we aimed to examine the ferret immune response to H7N9 influenza virus infection by analyzing leukocyte population variation associated with disease pathogenesis. While the day 6 ferret which showed worsened disease progression did exhibit the most severe lung pathology, the lack of viral antigen in and around these lesions (Supplementary Figure 1) means they cannot conclusively be classified as being caused by the influenza infection, and thus we are hesitant to classify disease presentation in this ferret as like a high pathogenicity infection based on the histopathology findings regardless of the increase in clinical signs. Highly pathogenic avian influenza virus infection in chickens but not ducks is associated with elevated host immune and pro-inflammatory responses abstract: As the recent outbreak of SARS-CoV-2 has highlighted, the threat of a pandemic event from zoonotic viruses, such as the deadly influenza A/H7N9 virus subtype, continues to be a major global health concern. H7N9 virus strains appear to exhibit greater disease severity in mammalian hosts compared to natural avian hosts, though the exact mechanisms underlying this are somewhat unclear. Knowledge of the H7N9 host-pathogen interactions have mainly been constrained to natural sporadic human infections. To elucidate the cellular immune mechanisms associated with disease severity and progression, we used a ferret model to closely resemble disease outcomes in humans following influenza virus infection. Intriguingly, we observed variable disease outcomes when ferrets were inoculated with the A/Anhui/1/2013 (H7N9) strain. We observed relatively reduced antigen-presenting cell activation in lymphoid tissues which may be correlative with increased disease severity. Additionally, depletions in CD8(+) T cells were not apparent in sick animals. This study provides further insight into the ways that lymphocytes maturate and traffic in response to H7N9 infection in the ferret model. url: https://www.ncbi.nlm.nih.gov/pubmed/33072098/ doi: 10.3389/fimmu.2020.559113 id: cord-319774-mkz7z38o author: Hou, Dongni title: High-Throughput Sequencing-Based Immune Repertoire Study during Infectious Disease date: 2016-08-31 words: 6126.0 sentences: 310.0 pages: flesch: 36.0 cache: ./cache/cord-319774-mkz7z38o.txt txt: ./txt/cord-319774-mkz7z38o.txt summary: The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. During the past two decades, however, technical advances in high-throughput sequencing (HTS), also known as next-generation sequencing (NGS), along with evolving bioinformatic and statistical tools, have provided a new approach capable of analyzing the immune repertoire at the single sequence level. The depth and comprehensiveness of high-throughput immune repertoire sequencing are greater than ever, and the enormous sequencing data of disease-specific TCR/BCR clones provide great potential for the revealing dynamic changes in clonality during infectious states. Decrease in the overall diversity of the immune repertoire have been observed after various antigen exposures, including HIV, influenza, and human herpes virus, which implies expansion of particular T/B cell clones (67, 88, 92, 93) . Pairing the heavy and light chains as an integrated antibody has been another challenge for HTS-based immune repertoire analysis. abstract: The selectivity of the adaptive immune response is based on the enormous diversity of T and B cell antigen-specific receptors. The immune repertoire, the collection of T and B cells with functional diversity in the circulatory system at any given time, is dynamic and reflects the essence of immune selectivity. In this article, we review the recent advances in immune repertoire study of infectious diseases, which were achieved by traditional techniques and high-throughput sequencing (HTS) techniques. HTS techniques enable the determination of complementary regions of lymphocyte receptors with unprecedented efficiency and scale. This progress in methodology enhances the understanding of immunologic changes during pathogen challenge and also provides a basis for further development of novel diagnostic markers, immunotherapies, and vaccines. url: https://doi.org/10.3389/fimmu.2016.00336 doi: 10.3389/fimmu.2016.00336 id: cord-030803-6i0e2zkd author: Hu, Wan-Chung title: A Framework of All Discovered Immunological Pathways and Their Roles for Four Specific Types of Pathogens and Hypersensitivities date: 2020-08-07 words: 3125.0 sentences: 216.0 pages: flesch: 49.0 cache: ./cache/cord-030803-6i0e2zkd.txt txt: ./txt/cord-030803-6i0e2zkd.txt summary: STAT5a and STAT5b have distinct target genes in immune responses (15) , and STAT5b is the transcription factor that induces Tfh. Tfh can induce B-cells to produce IgM antibodies and IL-21 produced by Tfh facilitates B cell isotype switching to IgG (16, 17) . Type 2 myeloid dendritic cells (CD141+ mDC2) are the antigen presenting cells Eradicable immune responses include TH1, TH2, TH17, and THαβ. Initiation of eradicable immunity also requires innate lymphoid cells to produce the initial cytokines that drive different immunological pathways. THαβ immune responses against self-antigens present as type 2 antibody-dependent cytotoxic hypersensitivity, such as the acute stage of myasthenia gravis or Graves'' disease (37) . The effector cells of TH1-like immune responses include suppressive macrophages (M2), ILC1, suppressive CD8 T cells (CD28-CD8+Treg), IgA1producing B-cells, iNKT1 cells, and IFN-γ-/TGF-β-producing CD4 T cells (24, 40, 56) . TH3 immune responses induce type 2 antibody-dependent cytotoxic hypersensitivity, including the chronic stage of Systemic Lupus Erythematosus (SLE) (69) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426516/ doi: 10.3389/fimmu.2020.01992 id: cord-003319-u88gznxq author: Huang, Weishan title: Beyond Type 1 Regulatory T Cells: Co-expression of LAG3 and CD49b in IL-10-Producing T Cell Lineages date: 2018-11-19 words: 6298.0 sentences: 313.0 pages: flesch: 53.0 cache: ./cache/cord-003319-u88gznxq.txt txt: ./txt/cord-003319-u88gznxq.txt summary: To determine whether co-expression of LAG3 and CD49b is exclusive to Foxp3 − Tr1 cell subset, we infected IL-10 GFP /Foxp3 RFP dual reporter mice with Nb, and analyzed the IL-10-producing T cells. Along with the model of parasitic infection shown in Figure 2 , our data suggest that co-expression of LAG3 and CD49b marks all IL-10-producing T cell lineages in the pulmonary system, and relative abundance of the marked T cell subsets is dependent on the type of immune response as shown in the disease models. Despite the shared feature of co-expression of LAG3 and CD49b by IL-10-producing Foxp3 + CD4 + , Foxp3 − CD4 + , and CD8 + T cells, we also observed interesting discrepancies in the proportional composition of these three IL-10 high T cell subsets that are all LAG3/CD49b double positive in the lung mucosa of different pulmonary inflammatory disease models, as well as in different anatomical locations in the same mice upon TCR activation in vivo. abstract: Type 1 regulatory CD4(+) T (Tr1) cells express high levels of the immunosuppressive cytokine IL-10 but not the master transcription factor Foxp3, and can suppress inflammation and promote immune tolerance. In order to identify and obtain viable Tr1 cells for research and clinical applications, co-expression of CD49b and LAG3 has been proposed as a unique surface signature for both human and mouse Tr1 cells. However, recent studies have revealed that this pattern of co-expression is dependent on the stimulating conditions and the differentiation stage of the CD4(+) T cells. Here, using an IL-10(GFP)/Foxp3(RFP) dual reporter transgenic murine model, we demonstrate that co-expression of CD49b and LAG3 is not restricted to the Foxp3(−) Tr1 cells, but is also observed in Foxp3(+) T regulatory (Treg) cells and CD8(+) T cells that produce IL-10. Our data indicate that IL-10-producing Tr1 cells, Treg cells and CD8(+) T cells are all capable of co-expressing LAG3 and CD49b in vitro following differentiation under IL-10-inducing conditions, and in vivo following pathogenic insult or infection in the pulmonary mucosa. Our findings urge caution in the use of LAG3/CD49b co-expression as sole markers to identify Tr1 cells, since it may mark IL-10-producing T cell lineages more broadly, including the Foxp3(−) Tr1 cells, Foxp3(+) Treg cells, and CD8(+) T cells. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252342/ doi: 10.3389/fimmu.2018.02625 id: cord-259131-36udb7uc author: Hunegnaw, Ruth title: Alveolar Macrophage Dysfunction and Increased PD-1 Expression During Chronic SIV Infection of Rhesus Macaques date: 2019-07-03 words: 7426.0 sentences: 376.0 pages: flesch: 46.0 cache: ./cache/cord-259131-36udb7uc.txt txt: ./txt/cord-259131-36udb7uc.txt summary: AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. In addition, the low proinflammatory cytokine response in chronic infection was not associated with an increase in IL-10-expressing AMs. To investigate AM activation, BAL cells obtained from naïve and acute and chronically infected macaques at weeks 2, 4, 8, 12, and 20 wpi, were incubated with native gp120 from R5 tropic SIV or LPS for 6 h, and intracellular expression of MIP-1β and IL-6 was assessed (Figures 3A,B) . Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals abstract: HIV infected individuals have been shown to be pre-disposed to pulmonary infections even while receiving anti-retroviral therapy. Alveolar macrophages (AMs) play a critical role in lung innate immunity, but contradictory results have been reported regarding their functionality following HIV infection. Here, using the SIV rhesus macaque model, we document the effect of SIV infection on the phenotypic and functional properties of AMs. Following infection with SIV(mac251), AMs in bronchoalveolar lavage (BAL) sampled over 2- to 20-weeks post-infection (wpi) were compared to those in BAL samples from naïve macaques. AM expression of proinflammatory cytokines TNF-α, IL-6, IL-1β, and chemokine RANTES drastically increased 2-wpi compared to AMs of naïve macaques (p < 0.0001 for all), but dropped significantly with progression to chronic infection. Phagocytic activity of AMs 2-and 4-wpi was elevated compared to AMs of naive animals (p = 0.0005, p = 0.0004, respectively) but significantly decreased by 12-wpi (p = 0.0022, p = 0.0019, respectively). By 20-wpi the ability of AMs from chronically infected animals to perform SIV-specific antibody-dependent phagocytosis (ADP) was also diminished (p = 0.028). Acute SIV infection was associated with increased FcγRIII expression which subsequently declined with disease progression. Frequency of FcγRIII(+) AMs showed a strong trend toward correlation with SIV-specific ADP, and at 2-wpi FcγRIII expression negatively correlated with viral load (r = −0.6819; p = 0.0013), suggesting a contribution to viremia control. Importantly, PD-1 was found to be expressed on AMs and showed a strong trend toward correlation with plasma viral load (r = 0.8266; p = 0.058), indicating that similar to over-expression on T-cells, PD-1 expression on AMs may also be associated with disease progression. Further, AMs predominantly expressed PD-L2, which remained consistent over the course of infection. PD-1 blockade enhanced SIV-specific ADP by AMs from chronic infection indicating that the PD-1/PD-L2 pathway may modulate functional activity of AMs at that stage. These findings provide new insight into the dynamics of SIV infection leading to AM dysfunction and alteration of pulmonary innate immunity. Our results suggest new pathways to exploit in developing therapies targeting pulmonary disease susceptibility in HIV-infected individuals. url: https://doi.org/10.3389/fimmu.2019.01537 doi: 10.3389/fimmu.2019.01537 id: cord-261367-i1n8x0uc author: Hwang, Ji Young title: Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date: 2020-09-25 words: 7609.0 sentences: 309.0 pages: flesch: 47.0 cache: ./cache/cord-261367-i1n8x0uc.txt txt: ./txt/cord-261367-i1n8x0uc.txt summary: Instead, mice with iBALT had reduced Th2-associated mRNA expression, less eosinophil recruitment to the lungs and airways, attenuated goblet cell hyperplasia and reduced mucus production following pulmonary sensitization and challenge with OVA. To test the effect of iBALT on the immune response to a pulmonary allergen, we administered LPS (or PBS) to neonatal mice as described above, allowed the mice to rest until they were 7 weeks old, then intranasally sensitized the iBALT and control groups with 100 µg OVA in combination with low dose (0.1 µg) LPS on days 49, 50, and 51 and challenged them on days 63, 64, 67, and 68 with 25 µg OVA ( Figure 1E ). Together, these data suggest that the spatial distribution of effector Th2 cells and Tregs is affected by the presence of iBALT (they cluster together), which may explain how iBALT and control mice can have similar numbers of Th2 cells in their lungs, but have so profoundly different outcomes in terms of eosinophil accumulation and histopathology. abstract: Inducible Bronchus Associated Lymphoid Tissue (iBALT) is an ectopic lymphoid tissue associated with severe forms of chronic lung diseases, including chronic obstructive pulmonary disease, rheumatoid lung disease, hypersensitivity pneumonitis and asthma, suggesting that iBALT may exacerbate these clinical conditions. However, despite the link between pulmonary pathology and iBALT formation, the role of iBALT in pathogenesis remains unknown. Here we tested whether the presence of iBALT in the lung prior to sensitization and challenge with a pulmonary allergen altered the biological outcome of disease. We found that the presence of iBALT did not exacerbate Th2 responses to pulmonary sensitization with ovalbumin. Instead, we found that mice with iBALT exhibited delayed Th2 accumulation in the lung, reduced eosinophil recruitment, reduced goblet cell hyperplasia and reduced mucus production. The presence of iBALT did not alter Th2 priming, but instead delayed the accumulation of Th2 cells in the lung following challenge and altered the spatial distribution of T cells in the lung. These results suggest that the formation of iBALT and sequestration of effector T cells in the context of chronic pulmonary inflammation may be a mechanism by which the immune system attenuates pulmonary inflammation and prevents excessive pathology. url: https://www.ncbi.nlm.nih.gov/pubmed/33101290/ doi: 10.3389/fimmu.2020.570661 id: cord-328763-hcbs20a0 author: Ifergan, Igal title: Potential for Targeting Myeloid Cells in Controlling CNS Inflammation date: 2020-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple Sclerosis (MS) is characterized by immune cell infiltration to the central nervous system (CNS) as well as loss of myelin. Characterization of the cells in lesions of MS patients revealed an important accumulation of myeloid cells such as macrophages and dendritic cells (DCs). Data from the experimental autoimmune encephalomyelitis (EAE) model of MS supports the importance of peripheral myeloid cells in the disease pathology. However, the majority of MS therapies focus on lymphocytes. As we will discuss in this review, multiple strategies are now in place to target myeloid cells in clinical trials. These strategies have emerged from data in both human and mouse studies. We discuss strategies targeting myeloid cell migration, growth factors and cytokines, biological functions (with a focus on miRNAs), and immunological activities (with a focus on nanoparticles). url: https://www.ncbi.nlm.nih.gov/pubmed/33123148/ doi: 10.3389/fimmu.2020.571897 id: cord-318418-uqxzds6g author: Inatomi, Takio title: Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition date: 2017-12-22 words: 4344.0 sentences: 219.0 pages: flesch: 46.0 cache: ./cache/cord-318418-uqxzds6g.txt txt: ./txt/cord-318418-uqxzds6g.txt summary: title: Dietary Probiotic Compound Improves Reproductive Performance of Porcine Epidemic Diarrhea Virus-Infected Sows Reared in a Japanese Commercial Swine Farm under Vaccine Control Condition Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan) to improve the health and reproductive performance of PED-infected sows. The aim of the present study was to evaluate the efficacy of the aforementioned probiotic compound mixed with peptide-zinc to improve the health and reproductive performance of PEDinfected lactating sows when administered along with a PED vaccine injection in Japan. Nonetheless, in the present work, probiotics supplementation significantly improved the concentration of total IgA and IgG in the milk of sows than did PED vaccination alone, possibly resulting from stimulation of gut immunity by bacteria in the administered probiotic compound (Figures 5A,B) . abstract: Lactogenic immunity transferred to piglets after inoculation of a live vaccine to pregnant sows was proved limited to control porcine epidemic diarrhea (PED). Hence, here we evaluated the efficacy of administration of a probiotic compound containing Bacillus mesentericus, Clostridium butyricum, and Enterococcus faecalis together with a commercial live-attenuated PED vaccine (Nisseiken PED Live Vaccine, Nisseiken, Tokyo, Japan) to improve the health and reproductive performance of PED-infected sows. Twenty pregnant sows in a PED-positive farm were equally divided into probiotics-administered (VP) and control (VC) sow groups. A commercial live-attenuated vaccine was injected as per the manufacturer’s instruction. The probiotic compound (15 g/day) was orally administered to VP from 6 weeks pre-parturition to 7 days post-parturition (ppd7). VP had a significantly higher body weight at ppd7 than VC (191 vs 186 kg; P < 0.05). At day 3 post-parturition (ppd3) (4.18 vs 3.63 kg/day) and ppd7 (5.14 vs 4.34 kg/day), milk produced by VP was significantly (P < 0.05) greater than that by VC. Total immunoglobulin (Ig)A and IgG concentrations at day 0 were significantly (P < 0.05) higher in whey of VP (1.9 and 6.6 g/dL, respectively) than in that of VC (1.7 and 6.1 g/dL, respectively). However, total IgG concentration in whey of VP and VC at ppd3 and ppd7 did not differ. Antibody titer was significantly higher at day 0 in serum of VP than it was that of VC (60 vs 37 in geometric mean; P < 0.05). Likewise, the antibody titer in whey of VP and VC was found to be similar at day 0 (416 vs 208 in geometric mean; P = 0.13). Consequently, VP had fewer days between weaning and return to estrus than did VC (7 vs 10 days; P < 0.05). Moreover, piglets of VP had a significantly (P < 0.05) higher litter weight at birth (9,252 g/litter) and a lower mortality (12%) during suckling than those of VC (8,686 g/litter and 28%, respectively). In summary, probiotic-supplemented, PED-vaccinated sows were healthier, transferred PED-specific antibodies via colostrum to piglets, had greater litter weight at birth, and reduced mortality during suckling. url: https://www.ncbi.nlm.nih.gov/pubmed/29312349/ doi: 10.3389/fimmu.2017.01877 id: cord-342776-hkjhqgie author: Jewett, Anahid title: The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions date: 2020-07-10 words: 3612.0 sentences: 159.0 pages: flesch: 41.0 cache: ./cache/cord-342776-hkjhqgie.txt txt: ./txt/cord-342776-hkjhqgie.txt summary: While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease. In particular, in the peripheral blood of patients that were infected with SARS, it was noted that there were significantly lower numbers of natural killer (NK) cells compared to healthy subjects (14) . As mentioned above the infectious agent of COVID-19 disease depletes NK cells in the peripheral blood, and potentially even in the lung tissues of patients, thereby, disabling and depleting the core immune effectors necessary to remove the virus and regulate uncontrolled immune activation. abstract: Coronavirus-induced disease-2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. This commentary outlines what is the reported literature thus far on the effect of virus on NK cells known to kill virally infected cells. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease. url: https://doi.org/10.3389/fimmu.2020.01692 doi: 10.3389/fimmu.2020.01692 id: cord-268438-bjs5oliw author: Jin, Yilin title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination date: 2019-12-03 words: 5040.0 sentences: 321.0 pages: flesch: 51.0 cache: ./cache/cord-268438-bjs5oliw.txt txt: ./txt/cord-268438-bjs5oliw.txt summary: title: Zebrafish TRIM25 Promotes Innate Immune Response to RGNNV Infection by Targeting 2CARD and RD Regions of RIG-I for K63-Linked Ubiquitination Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. In the present study, zebrafish TRIM25 (zbTRIM25) was involved in RGNNV infection and was identified as a positive mediator of RLR signaling pathway by binding to and ubiquitinating the caspase activation and recruitment domain (2CARD) and repressor domain (RD) regions of RIG-I, which is different with the findings in mammals. In mammals, previous reports showed that TRIM25 enhanced RLRs antiviral pathway by binding viral RNA-activated RIG-I to induce its K63-linked polyubiquitination and subsequent IFNs and ISGs production (26) . Here, we found that zbTRIM25 positively regulated RLR signaling pathway and facilitated zbRIG-I-mediated IFN 1 promoter activation, and overexpression of zbTRIM25 inhibited RGNNV infection, indicating the conservative antiviral properties of TRIM25 in fish and mammals. abstract: RIG-I-like receptors (RLRs) play important roles in response to virus infection by regulating host innate immune signaling pathways. Meanwhile, the RLR signaling pathway is also tightly regulated by host and virus to achieve the immune homeostasis between antiviral responses and virus survival. Here, we found that zebrafish TRIM25 (zbTRIM25) functioned as a positive regulator of RLR signaling pathway during red spotted grouper nervous necrosis virus (RGNNV) infection. Post-RGNNV infection, zbTRIM25 expression was obviously inhibited and ectopic expression of zbTRIM25 led to enhanced expression of RLR signaling pathway-related genes. Overexpression and knockdown analysis revealed that zbTRIM25 promoted zebrafish RIG-I (zbRIG-I)-mediated IFN signaling and inhibited RGNNV replication. Mechanistically, zbTRIM25 bound to zbRIG-I; in particular, the SPRY domain of zbTRIM25 interacted with the tandem caspase activation and recruitment domains (2CARD) and repressor domain (RD) regions of zbRIG-I. zbTRIM25 promoted the K63 polyubiquitination of 2CARD and RD regions of zbRIG-I. Furthermore, zbTRIM25-mediated zbRIG-I activation of IFN production was enhanced by K63-linked ubiquitin, indicating that zbTRIM25-mediated zbRIG-I polyubiquitination was essential for RIG-I-triggered IFN induction. In conclusion, these findings reveal a novel mechanism that zbTRIM25 positively regulates the innate immune response by targeting and promoting the K63-linked polyubiquitination of zbRIG-I. url: https://www.ncbi.nlm.nih.gov/pubmed/31849979/ doi: 10.3389/fimmu.2019.02805 id: cord-269170-9f460xbq author: Kaneko, Kazunari title: Our Evolving Understanding of Kawasaki Disease Pathogenesis: Role of the Gut Microbiota date: 2020-07-24 words: 4597.0 sentences: 248.0 pages: flesch: 35.0 cache: ./cache/cord-269170-9f460xbq.txt txt: ./txt/cord-269170-9f460xbq.txt summary: The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This perspective is illustrated in Figure 1 and can be explained as follows: [1] various factors during the in utero and postnatal period drive dysbiosis in young children; [2] dysbiosis results in reduced intestinal production of SCFAs including butyrate; [3] reduced levels of SCFAs in the gut cause an imbalance of Th17s/Tregs; and [4] individuals with Th17/Treg imbalances develop hypercytokinemia triggered by ubiquitous infectious agents(s), followed by KD (Figure 1) . abstract: Kawasaki disease (KD) was first described by Dr. Tomisaku Kawasaki in 1967. The etiology of KD has been studied comprehensively but remains largely unknown. The disease seems to result from the interplay of genetic and environmental susceptibility factors with infectious triggers, followed by a subsequent abnormal immune response characterized by increased levels of inflammatory cytokines and chemokines during the acute phase. Evidence has mounted to suggest that an imbalance between T helper 17 cells (Th17s) and regulatory T cells (Tregs) is associated with aberrant immune responses in KD. Recent advances in culture-independent techniques for detection and identification of intestinal commensal bacteria enabled the discovery that Th17 and Treg differentiation are regulated by short chain fatty acids (SCFAs), in particular butyrate, produced by the gut microbiota. This finding provided a mechanistic link between dysbiosis, defined as changes in the composition of the gut microbiota, and various inflammatory diseases. On this basis, we propose that dysbiosis, with reduced production of SCFAs leading to imbalances of Th17s/Tregs, could be involved in the etiology of KD. A pilot study supported this hypothesis, as only fecal concentrations of butyrate were significantly reduced in KD patients among SCFAs. This evolving perspective prompted us to undertake metagenomic analyses of bacterial DNA from the feces of KD patients who were antibiotic-naïve at diagnosis. Simultaneous measurements of Th17s/Tregs in peripheral blood and SCFA concentrations in feces would provide valuable information regarding the association between dysbiosis and dysregulated immune responses in KD. url: https://www.ncbi.nlm.nih.gov/pubmed/32793240/ doi: 10.3389/fimmu.2020.01616 id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic. url: https://doi.org/10.3389/fimmu.2020.570927 doi: 10.3389/fimmu.2020.570927 id: cord-298604-tn8hc6jv author: Khawaja, Akif A. title: Identification of a Novel HIF-1α-α(M)β(2) Integrin-NET Axis in Fibrotic Interstitial Lung Disease date: 2020-10-15 words: 7971.0 sentences: 420.0 pages: flesch: 40.0 cache: ./cache/cord-298604-tn8hc6jv.txt txt: ./txt/cord-298604-tn8hc6jv.txt summary: Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. We measured neutrophil adhesion to primary human endothelial cells in the absence or presence of PMA (a general integrin activator) or LPS (to mimic infectious stimuli), stimuli that induce NETs via distinct pathways (42) . We report, for the first time, that neutrophils and endothelial cells in ILD lung biopsies display HIF-1α expression and provide evidence of the extracellular release of nuclear DNA, citrullinated histones and MPO, indicative of NET formation in the ILD lung. abstract: Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) particularly in the most severe form, idiopathic pulmonary fibrosis (IPF), although the underlying mechanisms remain unclear. Neutrophil function is modulated by numerous factors, including integrin activation, inflammatory cytokines and hypoxia. Hypoxia has an important role in inflammation and may also contribute to pulmonary disease. We aimed to determine how neutrophil activation occurs in ILD and the relative importance of hypoxia. Using lung biopsies and bronchoalveolar lavage (BAL) fluid from ILD patients we investigated the extent of hypoxia and neutrophil activation in ILD lungs. Then we used ex vivo neutrophils isolated from healthy volunteers and BAL from patients with ILD and non-ILD controls to further investigate aberrant neutrophil activation in hypoxia and ILD. We demonstrate for the first time using intracellular staining, HIF-1α stabilization in neutrophils and endothelial cells in ILD lung biopsies. Hypoxia enhanced both spontaneous (+1.31-fold, p < 0.05) and phorbol 12-myristate 13-acetate (PMA)-induced (+1.65-fold, p < 0.001) neutrophil extracellular trap (NET) release, neutrophil adhesion (+8.8-fold, <0.05), and trans-endothelial migration (+1.9-fold, p < 0.05). Hypoxia also increased neutrophil expression of the α(M) (+3.1-fold, p < 0.001) and α(X) (+1.6-fold, p < 0.01) integrin subunits. Interestingly, NET formation was induced by α(M)β(2) integrin activation and prevented by cation chelation. Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. In conclusion, HIF-1α upregulation may augment neutrophil recruitment and activation within the lung interstitium through activation of β(2) integrins. Our results identify a novel HIF-1α- α(M)β(2) integrin axis in NET formation for future exploration in therapeutic approaches to fibrotic ILD. url: https://doi.org/10.3389/fimmu.2020.02190 doi: 10.3389/fimmu.2020.02190 id: cord-280941-ds6x0yym author: Kim, Young-Seok title: Chaperna-Mediated Assembly of Ferritin-Based Middle East Respiratory Syndrome-Coronavirus Nanoparticles date: 2018-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The folding of monomeric antigens and their subsequent assembly into higher ordered structures are crucial for robust and effective production of nanoparticle (NP) vaccines in a timely and reproducible manner. Despite significant advances in in silico design and structure-based assembly, most engineered NPs are refractory to soluble expression and fail to assemble as designed, presenting major challenges in the manufacturing process. The failure is due to a lack of understanding of the kinetic pathways and enabling technical platforms to ensure successful folding of the monomer antigens into regular assemblages. Capitalizing on a novel function of RNA as a molecular chaperone (chaperna: chaperone + RNA), we provide a robust protein-folding vehicle that may be implemented to NP assembly in bacterial hosts. The receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) was fused with the RNA-interaction domain (RID) and bacterioferritin, and expressed in Escherichia coli in a soluble form. Site-specific proteolytic removal of the RID prompted the assemblage of monomers into NPs, which was confirmed by electron microscopy and dynamic light scattering. The mutations that affected the RNA binding to RBD significantly increased the soluble aggregation into amorphous structures, reducing the overall yield of NPs of a defined size. This underscored the RNA-antigen interactions during NP assembly. The sera after mouse immunization effectively interfered with the binding of MERS-CoV RBD to the cellular receptor hDPP4. The results suggest that RNA-binding controls the overall kinetic network of the antigen folding pathway in favor of enhanced assemblage of NPs into highly regular and immunologically relevant conformations. The concentration of the ion Fe(2+), salt, and fusion linker also contributed to the assembly in vitro, and the stability of the NPs. The kinetic “pace-keeping” role of chaperna in the super molecular assembly of antigen monomers holds promise for the development and delivery of NPs and virus-like particles as recombinant vaccines and for serological detection of viral infections. url: https://doi.org/10.3389/fimmu.2018.01093 doi: 10.3389/fimmu.2018.01093 id: cord-338498-3238fz73 author: Kleen, Thomas-Oliver title: Mitigating Coronavirus Induced Dysfunctional Immunity for At-Risk Populations in COVID-19: Trained Immunity, BCG and “New Old Friends” date: 2020-09-04 words: 12523.0 sentences: 559.0 pages: flesch: 39.0 cache: ./cache/cord-338498-3238fz73.txt txt: ./txt/cord-338498-3238fz73.txt summary: Bacterial "new old friends" such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called "trained immunity." Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other "new old friends." One recent example of the need for continued vigilance is a study using Chinese macaques indicating cause for concern by showing that vaccine-induced, S-specific immunity in the form of anti-spike IgG resulted in severe ALI by skewing macrophage responses during subsequent, acute infection with closely related SARS-CoV (139) . abstract: The novel, highly contagious coronavirus SARS-CoV-2 spreads rapidly throughout the world, leading to a deadly pandemic of a predominantly respiratory illness called COVID-19. Safe and effective anti-SARS-CoV-2 vaccines are urgently needed. However, emerging immunological observations show hallmarks of significant immunopathological characteristics and dysfunctional immune responses in patients with COVID-19. Combined with existing knowledge about immune responses to other closely related and highly pathogenic coronaviruses, this could forebode significant challenges for vaccine development, including the risk of vaccine failure. Animal data from earlier coronavirus vaccine efforts indicate that elderly people, most at risk from severe COVID-19 disease, could be especially at risk from immunopathologic responses to novel coronavirus vaccines. Bacterial “new old friends” such as Bacille Calmette-Guérin (BCG) or Mycobacterium obuense have the ability to elevate basal systemic levels of type 1 cytokines and immune cells, correlating with increased protection against diverse and unrelated infectious agents, called “trained immunity.” Here we describe dysfunctional immune responses induced by coronaviruses, representing potentially difficult to overcome obstacles to safe, effective vaccine development for COVID-19, and outline how trained immunity could help protect high risk populations through immunomodulation with BCG and other “new old friends.” url: https://doi.org/10.3389/fimmu.2020.02059 doi: 10.3389/fimmu.2020.02059 id: cord-268511-dx2cqqt5 author: Kunkl, Martina title: CD28 Autonomous Signaling Orchestrates IL-22 Expression and IL-22-Regulated Epithelial Barrier Functions in Human T Lymphocytes date: 2020-10-14 words: 6320.0 sentences: 330.0 pages: flesch: 49.0 cache: ./cache/cord-268511-dx2cqqt5.txt txt: ./txt/cord-268511-dx2cqqt5.txt summary: We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. However, although IL-6 itself is able to prime IL-22 production in activated human CD4 + T cells (41) , stimulation of CD4 + T cells with IL-6 alone is not sufficient for up-regulating IL-22 gene expression ( Figure 1G ) but requires a second signal delivered by CD28. During CD28 stimulation, RelA/NF-kB and IL-6-associated STAT3 cooperate for inducing IL-22 expression and secretion ( Figure 3 ) that in turn acts on epithelial cells by promoting the up-regulation of MUC1 ( Figure 4) . abstract: IL-22 is a member of the IL-10 cytokine family involved in host protection against extracellular pathogens, by promoting epithelial cell regeneration and barrier functions. Dysregulation of IL-22 production has also frequently been observed in acute respiratory distress syndrome (ARDS) and several chronic inflammatory and autoimmune diseases. We have previously described that human CD28, a crucial co-stimulatory receptor necessary for full T cell activation, is also able to act as a TCR independent signaling receptor and to induce the expression of IL-17A and inflammatory cytokines related to Th17 cells, which together with Th22 cells represent the main cellular source of IL-22. Here we characterized the role of CD28 autonomous signaling in regulating IL-22 expression in human CD4(+) T cells. We show that CD28 stimulation in the absence of TCR strongly up-regulates IL-22 gene expression and secretion. As recently observed for IL-17A, we also found that CD28-mediated regulation of IL-22 transcription requires the cooperative activities of both IL-6-activated STAT3 and RelA/NF-κB transcription factors. CD28-mediated IL-22 production also promotes the barrier functions of epithelial cells by inducing mucin and metalloproteases expression. Finally, by using specific inhibitory drugs, we also identified CD28-associated class 1A phosphatidylinositol 3-kinase (PI3K) as a pivotal mediator of CD28-mediated IL-22 expression and IL-22–dependent epithelial cell barrier functions. url: https://doi.org/10.3389/fimmu.2020.590964 doi: 10.3389/fimmu.2020.590964 id: cord-279105-e2zjxjox author: Lee, Cheryl Yi-Pin title: Serological Approaches for COVID-19: Epidemiologic Perspective on Surveillance and Control date: 2020-04-24 words: 3872.0 sentences: 212.0 pages: flesch: 44.0 cache: ./cache/cord-279105-e2zjxjox.txt txt: ./txt/cord-279105-e2zjxjox.txt summary: With the limitations of qRT-PCR, immunoassays may offer another FIGURE 2 | Schematic illustration on the window period of detection for either viral RNA or antibodies in SARS-CoV-2-infected individuals. However, interestingly, one study demonstrated that longitudinal profiling of both antibodies in a population of 63 COVID-19 patients showed no specific chronological order in terms of IgM and IgG seroconversion (10) , which was also observed in patients infected with SARS-CoV and another human coronavirus, Middle East Respiratory Syndrome coronavirus (MERS-CoV) (22, 23) . These findings on SARS-CoV-2-specific antibodies seroconversion against the S viral protein suggest the importance to test for both IgM and IgG antibodies to confirm a positive infection. With the availability of immunoassays utilizing various coronavirus structural proteins, the use of more than one different antigen-based serological approach may be essential to establish a true positive SARS-CoV-2 infection. abstract: Since December 2019, the novel coronavirus, SARS-CoV-2, has garnered global attention due to its rapid transmission, which has infected more than two million people worldwide. Early detection of SARS-CoV-2 is one of the crucial interventions to control virus spread and dissemination. Molecular assays have been the gold standard to directly detect for the presence of viral genetic material in infected individuals. However, insufficient viral RNA at the point of detection may lead to false negative results. As such, it is important to also employ immune-based assays to determine one's exposure to SARS-CoV-2, as well as to assist in the surveillance of individuals with prior exposure to SARS-CoV-2. Within a span of 4 months, extensive studies have been done to develop serological systems to characterize the antibody profiles, as well as to identify and generate potentially neutralizing antibodies during SARS-CoV-2 infection. The vast diversity of novel findings has added value to coronavirus research, and a strategic consolidation is crucial to encompass the latest advances and developments. This review aims to provide a concise yet extensive collation of current immunoassays for SARS-CoV-2, while discussing the strengths, limitations and applications of antibody detection in SARS-CoV-2 research and control. url: https://www.ncbi.nlm.nih.gov/pubmed/32391022/ doi: 10.3389/fimmu.2020.00879 id: cord-003545-corvd5cs author: Li, Chen title: Fish Autophagy Protein 5 Exerts Negative Regulation on Antiviral Immune Response Against Iridovirus and Nodavirus date: 2019-03-19 words: 4512.0 sentences: 258.0 pages: flesch: 45.0 cache: ./cache/cord-003545-corvd5cs.txt txt: ./txt/cord-003545-corvd5cs.txt summary: The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV). Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs. In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition. Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle. To analyze the gene expression profiles in response to different viral infections, the transcription levels of EcAtg5 were examined in RGNNV or SGIV infected cells. The results showed that EcAtg5 plays crucial roles in virus replication via promoting autophagy, down-regulating antiviral IFN responses, and affecting cell cycle. abstract: Autophagy is an important biological activity that maintains homeostasis in eukaryotic cells. However, little is known about the functions of fish autophagy-related genes (Atgs). In this study, we cloned and characterized Atg5, a key gene in the autophagy gene superfamily, from orange-spotted grouper (Epinephelus coioides) (EcAtg5). EcAtg5 encoded a 275-amino acid protein that shared 94 and 81% identity to seabass (Lates calcarifer) and humans (Homo sapiens), respectively. The transcription level of EcAtg5 was significantly increased in cells infected with red-spotted grouper nervous necrosis virus (RGNNV). In cells infected with Singapore grouper iridovirus (SGIV), EcAtg5 expression declined during the early stage of infection and increased in the late stage. Fluorescence microscopy revealed that EcAtg5 mainly localized with a dot-like pattern in the cytoplasm of grouper cells. Overexpression of EcAtg5 significantly increased the replication of RGNNV and SGIV at different levels of detection, as indicated by increased severity of the cytopathic effect, transcription levels of viral genes, and levels of viral proteins. Knockdown of EcAtg5 decreased the replication of RGNNV and SGIV. Further studies showed that overexpression EcAtg5 activated autophagy, decreased expression levels of interferon related cytokines or effectors and pro-inflammatory factors, and inhibited the activation of nuclear factor κB, IFN-sensitive response element, and IFNs. In addition, ectopic expression of EcAtg5 affected cell cycle progression by hindering the G1/S transition. Taken together, our results demonstrated that fish Atg5 exerted a crucial role in virus replication by promoting autophagy, down-regulating antiviral IFN responses, and affecting the cell cycle. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433989/ doi: 10.3389/fimmu.2019.00517 id: cord-317797-h229skaq author: Li, Conglei title: Crosstalk Between Platelets and Microbial Pathogens date: 2020-08-07 words: 7628.0 sentences: 409.0 pages: flesch: 33.0 cache: ./cache/cord-317797-h229skaq.txt txt: ./txt/cord-317797-h229skaq.txt summary: For example, thrombocytopenia in children following varicella zoster virus infection first described antigenic mimicry for some microbial pathogens that encompass host generation of crossreactive antibodies to certain glycoproteins (e.g., GPIIIa) on the platelet surface, resulting in accelerated platelet clearance (117) . In addition to the effects on platelet count and function, microbial pathogens impact the host auto-and alloimmune response to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia (ITP), and fetal and neonatal alloimmune thrombocytopenia (FNAIT) (99-101) (Figure 3) . C-reactive protein is markedly upregulated during acute infections and inflammation (178) , and it has been shown that C-reactive protein, via binding to platelet phosphorylcholine residues, enhanced the IgG-mediated phagocytic responses against platelets and thereby thrombocytopenia, which has implications in the pathogenesis of both ITP and FNAIT (123, 124) . abstract: Platelets, small anucleate cells circulating in the blood, are critical mediators in haemostasis and thrombosis. Interestingly, recent studies demonstrated that platelets contain both pro-inflammatory and anti-inflammatory molecules, equipping platelets with immunoregulatory function in both innate and adaptive immunity. In the context of infectious diseases, platelets are involved in early detection of invading microorganisms and are actively recruited to sites of infection. Platelets exert their effects on microbial pathogens either by direct binding to eliminate or restrict dissemination, or by shaping the subsequent host immune response. Reciprocally, many invading microbial pathogens can directly or indirectly target host platelets, altering platelet count or/and function. In addition, microbial pathogens can impact the host auto- and alloimmune responses to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. In this review, we discuss the mechanisms that contribute to the bidirectional interactions between platelets and various microbial pathogens, and how these interactions hold relevant implications in the pathogenesis of many infectious diseases. The knowledge obtained from “well-studied” microbes may also help us understand the pathogenesis of emerging microbes, such as SARS-CoV-2 coronavirus. url: https://doi.org/10.3389/fimmu.2020.01962 doi: 10.3389/fimmu.2020.01962 id: cord-015254-xtox2rxs author: Li, Hao-Ling title: C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood–Spinal Cord Barrier date: 2020-03-20 words: 4506.0 sentences: 221.0 pages: flesch: 44.0 cache: ./cache/cord-015254-xtox2rxs.txt txt: ./txt/cord-015254-xtox2rxs.txt summary: We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. In this study, we examined the integrity of the BSCB and the migration of circulating immune cells into the spinal cord after chronic constriction injury (CCI) of the sciatic nerve, which induces neuropathic pain. To the best of our knowledge, it is the first study to report that blocking CXCL10/CXCR3 signaling attenuates the increases in BSCB permeability and T cell infiltration of the spinal cord induced by peripheral nerve injury. Previous studies have indicated that increased BSCB permeability is a prerequisite for immune cell infiltration of the spinal cord during the development of neuropathic pain (41) , and we found that blocking CXCL10/CXCR3 signaling with anti-CXCL10 antibodies reduced the BSCB''s permeability to NaFlu, which suggests that CXCL10/CXCR3 signaling plays a critical role in CCI-induced BSCB dysfunction. abstract: Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood–spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXCR3 activation, BSCB disruption, and mechanical hyperalgesia. CCI-induced BSCB disruption enabled circulating T cells to migrate into the spinal parenchyma. Intrathecal administration of an anti-CXCL10 antibody not only attenuated CCI-induced hyperalgesia, but also reduced BSCB permeability, suggesting that CXCL10 acts as a key regulator of BSCB integrity. Moreover, T cell migration may play a critical role in the neuroimmune interactions involved in the pathogenesis of CCI-induced neuropathic pain. Our results highlight CXCL10 as a new potential drug target for the treatment of nerve injury–induced neuropathic pain. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098954/ doi: 10.3389/fimmu.2020.00477 id: cord-254192-86ksgl5t author: Li, Liang title: IFN-Lambda 3 Mediates Antiviral Protection Against Porcine Epidemic Diarrhea Virus by Inducing a Distinct Antiviral Transcript Profile in Porcine Intestinal Epithelia date: 2019-10-17 words: 7233.0 sentences: 324.0 pages: flesch: 50.0 cache: ./cache/cord-254192-86ksgl5t.txt txt: ./txt/cord-254192-86ksgl5t.txt summary: Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In this study, we comprehensively compared the transcriptional profiling of IFN-λ3-and IFN-α-induced genes in a porcine intestinal epithelial cell line (IPEC-J2) and verified the RNA-Seq results by reverse transcriptase quantitative PCR (RT-qPCR) in vitro, and further confirmed the transcriptional profile difference in crypt-derived porcine enteroids. abstract: Type III interferon-lambda (IFN-λ) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-λ more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-λ3 exerts a more potent effect than IFN-λ1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-λ3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In contrast, IFN-α only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-λ3. A transcriptional enrichment analysis indicated that IFN-λ3 or IFN-α regulates multiple cellular processes and that IFN-λ3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-α. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-λ3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-λ3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-α and strongly elicits a set of genes responsible for the antiviral activity of IFN-λ3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection. url: https://doi.org/10.3389/fimmu.2019.02394 doi: 10.3389/fimmu.2019.02394 id: cord-255578-0ltb9dpa author: Li, Xiangru title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 words: 6400.0 sentences: 404.0 pages: flesch: 55.0 cache: ./cache/cord-255578-0ltb9dpa.txt txt: ./txt/cord-255578-0ltb9dpa.txt summary: title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. In this study, Cfhr1 was deleted on C57BL/6 mouse to study the function of FHR-E on AP and the effect of FHR-E deficiency on LPS-induced sepsis. abstract: Alternative complement pathway (AP) plays an important role in the development of sepsis, which is life threatening. Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. However, the underlying mechanism of the disease development is largely unknown. There is no report on CFHR1 gene knockout in any animal infection model and its function in vivo is still unclear. Here, a Cfhr1 knockout mouse was generated for investigating AP in sepsis and sepsis-induced acute kidney injury (AKI). We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. This study revealed the function of FHR-E in vivo, which may further provide hints to the pathogenesis of FHR-1 deficiency-related diseases by enhancing LPS-induced AP activation. url: https://www.ncbi.nlm.nih.gov/pubmed/32636836/ doi: 10.3389/fimmu.2020.01123 id: cord-341513-e6p3lrlf author: Li, Yunchuan title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection date: 2017-09-29 words: 6136.0 sentences: 341.0 pages: flesch: 47.0 cache: ./cache/cord-341513-e6p3lrlf.txt txt: ./txt/cord-341513-e6p3lrlf.txt summary: title: Microarray Analysis Identifies the Potential Role of Long Non-Coding RNA in Regulating Neuroinflammation during Japanese Encephalitis Virus Infection To determine the role of lncRNAs in inflammatory cytokine production, the cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. To examine the role of lncRNA E52329 and N54010 in regulating the kinase activity of MKK4/JNK pathway, BV2 cells were transfected with siE52329, siN54010 or non-specific control siRNA, and then infected with JEV. The results of our study reveal the first experimental evidence demonstrating the complex regulation of lncRNAs by JEV infection in mice brain and microglial cells. Third, the integration of microarray platform, quantitative real-time PCR, GO analysis, pathways analysis, and lncRNA-mRNA coexpression network analysis has allowed us to conduct an active comparative genomics and bioinformatics study to reveal host lncRNAs expression patterns associated with JEV infection. abstract: Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis worldwide. JEV-induced neuroinflammation is characterized by profound neuronal cells damage accompanied by activation of glial cells. Albeit long non-coding RNAs (lncRNAs) have been emerged as important regulatory RNAs with profound effects on various biological processes, it is unknown how lncRNAs regulate JEV-induced inflammation. Here, using microarray approach, we identified 618 lncRNAs and 1,007 mRNAs differentially expressed in JEV-infected mice brain. The functional annotation analysis revealed that differentially regulated transcripts were predominantly involved in various signaling pathways related to host immune and inflammatory responses. The lncRNAs with their potential to regulate JEV-induced inflammatory response were identified by constructing the lncRNA-mRNA coexpression network. Furthermore, silencing of the two selected lncRNAs (E52329 and N54010) resulted in reducing the phosphorylation of JNK and MKK4, which are known to be involved during inflammatory response. Collectively, we first demonstrated the transcriptomic landscape of lncRNAs in mice brain infected with JEV and analyzed the coexpression network of differentially regulated lncRNAs and mRNAs during JEV infection. Our results provide a better understanding of the host response to JEV infection and suggest that the identified lncRNAs may be used as potential therapeutic targets for the management of Japanese encephalitis. url: https://www.ncbi.nlm.nih.gov/pubmed/29033949/ doi: 10.3389/fimmu.2017.01237 id: cord-273505-pcsw3vmx author: Liu, Xiaosheng title: High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects date: 2020-07-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19. url: https://doi.org/10.3389/fimmu.2020.01660 doi: 10.3389/fimmu.2020.01660 id: cord-284156-btb4oodz author: Liu, Yiliu title: Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity date: 2017-01-03 words: 7021.0 sentences: 397.0 pages: flesch: 38.0 cache: ./cache/cord-284156-btb4oodz.txt txt: ./txt/cord-284156-btb4oodz.txt summary: Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. They function as cytoplasmic sensors for the recognition of a variety of RNA viruses and subsequent activation of downstream signaling to drive type I IFN production and antiviral gene expressions. (c) Interactions between RIG-I-TRIM25 complex and 14-3-3ϵ promote RIG-I translocation to mitochondrial mitochondrial antiviral signaling protein (MAVS) for downstream signaling, leading to interferon production. Protein purification and mass spectrometry analysis identified that phosphorylation of Thr170 in the CARDs antagonizes RIG-I signaling by inhibiting TRIM25-mediated Lys172 ubiquitination and MAVS binding (68) . Ebola virus VP35 protein binds double-stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling Inhibition of dengue and chikungunya virus infections by RIG-I-mediated type I interferon-independent stimulation of the innate antiviral response abstract: Innate immunity is the first line of defense against invading pathogens. Rapid and efficient detection of pathogen-associated molecular patterns via pattern-recognition receptors is essential for the host to mount defensive and protective responses. Retinoic acid-inducible gene-I (RIG-I) is critical in triggering antiviral and inflammatory responses for the control of viral replication in response to cytoplasmic virus-specific RNA structures. Upon viral RNA recognition, RIG-I recruits the mitochondrial adaptor protein mitochondrial antiviral signaling protein, which leads to a signaling cascade that coordinates the induction of type I interferons (IFNs), as well as a large variety of antiviral interferon-stimulated genes. The RIG-I activation is tightly regulated via various posttranslational modifications for the prevention of aberrant innate immune signaling. By contrast, viruses have evolved mechanisms of evasion, such as sequestrating viral structures from RIG-I detections and targeting receptor or signaling molecules for degradation. These virus–host interactions have broadened our understanding of viral pathogenesis and provided insights into the function of the RIG-I pathway. In this review, we summarize the recent advances regarding RIG-I pathogen recognition and signaling transduction, cell-intrinsic control of RIG-I activation, and the viral antagonism of RIG-I signaling. url: https://www.ncbi.nlm.nih.gov/pubmed/28096803/ doi: 10.3389/fimmu.2016.00662 id: cord-003368-f8f2utzx author: Lutterberg, Karina title: A Functionally Different Immune Phenotype in Cattle Is Associated With Higher Mastitis Incidence date: 2018-12-06 words: 5053.0 sentences: 287.0 pages: flesch: 46.0 cache: ./cache/cord-003368-f8f2utzx.txt txt: ./txt/cord-003368-f8f2utzx.txt summary: After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. As other authors claimed the possibility of a genetic predisposition of BNP dams for production of BNP inducing alloantibodies (22) (23) (24) , our studies focused on investigating a general difference in immune responses between PregSure BVD vaccinated control cows and BNP donors. In in vitro proliferation assays with T cell mitogen ConA we observed that 22% of the unvaccinated cows reacted similar to BNP dams by showing a hyperproliferative reaction to ConA (immune deviant (ID) phenotype; Figure 6A , reaction difference ID to controls or BNP to controls, * * * * p < 0.0001). abstract: A novel vaccine against bovine viral diarrhea (BVD) induced pathogenic antibody production in 5–10% of BVD-vaccinated cows. Transfer of these antibodies via colostrum caused Bovine neonatal pancytopenia (BNP) in calves, with a lethality rate of 90%. The exact immunological mechanisms behind the onset of BNP are not fully understood to date. To gain further insight into these mechanisms, we analyzed the immune proteome from alloreactive antibody producers (BNP cows) and non-responders. After in vitro stimulation of peripheral blood derived lymphocytes (PBL), we detected distinctly deviant expression levels of several master regulators of immune responses in BNP cells, pointing to a changed immune phenotype with severe dysregulation of immune response in BNP cows. Interestingly, we also found this response pattern in 22% of non-BVD-vaccinated cows, indicating a genetic predisposition of this immune deviant (ID) phenotype in cattle. We additionally analyzed the functional correlation of the ID phenotype with 10 health parameters and 6 diseases in a retrospective study over 38 months. The significantly increased prevalence of mastitis among ID cows emphasizes the clinical relevance of this deviant immune response and its potential impact on the ability to fight infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291514/ doi: 10.3389/fimmu.2018.02884 id: cord-297790-tpjxt0w5 author: Mandl, Judith N. title: Going to Bat(s) for Studies of Disease Tolerance date: 2018-09-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A majority of viruses that have caused recent epidemics with high lethality rates in people, are zoonoses originating from wildlife. Among them are filoviruses (e.g., Marburg, Ebola), coronaviruses (e.g., SARS, MERS), henipaviruses (e.g., Hendra, Nipah) which share the common features that they are all RNA viruses, and that a dysregulated immune response is an important contributor to the tissue damage and hence pathogenicity that results from infection in humans. Intriguingly, these viruses also all originate from bat reservoirs. Bats have been shown to have a greater mean viral richness than predicted by their phylogenetic distance from humans, their geographic range, or their presence in urban areas, suggesting other traits must explain why bats harbor a greater number of zoonotic viruses than other mammals. Bats are highly unusual among mammals in other ways as well. Not only are they the only mammals capable of powered flight, they have extraordinarily long life spans, with little detectable increases in mortality or senescence until high ages. Their physiology likely impacted their history of pathogen exposure and necessitated adaptations that may have also affected immune signaling pathways. Do our life history traits make us susceptible to generating damaging immune responses to RNA viruses or does the physiology of bats make them particularly tolerant or resistant? Understanding what immune mechanisms enable bats to coexist with RNA viruses may provide critical fundamental insights into how to achieve greater resilience in humans. url: https://doi.org/10.3389/fimmu.2018.02112 doi: 10.3389/fimmu.2018.02112 id: cord-320663-xypg6evo author: Market, Marisa title: Flattening the COVID-19 Curve With Natural Killer Cell Based Immunotherapies date: 2020-06-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Natural Killer (NK) cells are innate immune responders critical for viral clearance and immunomodulation. Despite their vital role in viral infection, the contribution of NK cells in fighting SARS-CoV-2 has not yet been directly investigated. Insights into pathophysiology and therapeutic opportunities can therefore be inferred from studies assessing NK cell phenotype and function during SARS, MERS, and COVID-19. These studies suggest a reduction in circulating NK cell numbers and/or an exhausted phenotype following infection and hint toward the dampening of NK cell responses by coronaviruses. Reduced circulating NK cell levels and exhaustion may be directly responsible for the progression and severity of COVID-19. Conversely, in light of data linking inflammation with coronavirus disease severity, it is necessary to examine NK cell potential in mediating immunopathology. A common feature of coronavirus infections is that significant morbidity and mortality is associated with lung injury and acute respiratory distress syndrome resulting from an exaggerated immune response, of which NK cells are an important component. In this review, we summarize the current understanding of how NK cells respond in both early and late coronavirus infections, and the implication for ongoing COVID-19 clinical trials. Using this immunological lens, we outline recommendations for therapeutic strategies against COVID-19 in clearing the virus while preventing the harm of immunopathological responses. url: https://doi.org/10.3389/fimmu.2020.01512 doi: 10.3389/fimmu.2020.01512 id: cord-272491-a84pahdr author: Maron-Gutierrez, Tatiana title: Cell-Free Therapies: Novel Approaches for COVID-19 date: 2020-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://doi.org/10.3389/fimmu.2020.583017 doi: 10.3389/fimmu.2020.583017 id: cord-252568-b8sbvy0g author: Marques Neto, Lázaro Moreira title: Role of Metallic Nanoparticles in Vaccinology: Implications for Infectious Disease Vaccine Development date: 2017-03-08 words: 5317.0 sentences: 260.0 pages: flesch: 39.0 cache: ./cache/cord-252568-b8sbvy0g.txt txt: ./txt/cord-252568-b8sbvy0g.txt summary: There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. However, many NPs have been shown to stimulate immune responses, including cell recruitment, activation of antigen (Ag)-presenting cells (APCs), and induction of cytokine and chemokine release. Among the vaccines targeting extracellular bacteria and toxin, two were formulated with lipopolysaccharide (LPS) in glycopeptide Ag. The use of glycoantigen and LPS can trigger an intense response through TLR4 and B cell receptor activation; the presence of gold NPs (AuNPs) may have minimal influence on this response. To understand the possible uses of MeNPs as platforms for vaccines against infectious diseases, analysis is needed of the impact of different physicochemical characteristics of NPs on the innate immune response (Figure 1) . abstract: Subunit vaccines are safer but less immunogenic than live-attenuated vaccines or whole cell inactivated vaccines. Adjuvants are used to enhance and modulate antigen (Ag) immunogenicity, aiming to induce a protective and long-lasting immune response. Several molecules and formulations have been studied for their adjuvanticity, but only seven have been approved to formulate human vaccines. Metallic nanoparticles (MeNPs), particularly those containing gold and iron oxides, are widely used in medicine for diagnosis and therapy and have been used as carriers for drugs and vaccines. However, little is known about the immune response elicited by MeNPs or about their importance in the development of new vaccines. There is evidence that these particles display adjuvant characteristics, promoting cell recruitment, antigen-presenting cell activation, cytokine production, and inducing a humoral immune response. This review focuses on the characteristics of MeNPs that could facilitate the induction of a cellular immune response, particularly T-helper 1 and T-helper 17, and their potential functions as adjuvants for subunit vaccines. url: https://www.ncbi.nlm.nih.gov/pubmed/28337198/ doi: 10.3389/fimmu.2017.00239 id: cord-306600-cxz8hf9q author: Matarazzo, Laura title: Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia date: 2019-04-09 words: 6540.0 sentences: 316.0 pages: flesch: 34.0 cache: ./cache/cord-306600-cxz8hf9q.txt txt: ./txt/cord-306600-cxz8hf9q.txt summary: Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. pneumoniae lung infection, we recently demonstrated that combination treatment with mucosally administered flagellin and an orally or intraperitoneally administered low-dose (i.e., subtherapeutic) antibiotic is more effective than the antibiotic alone (i.e., with a lower bacterial load in the lung, and a lower mortality rate). Our data showed that several antimicrobial peptides (S100A9), cytokines (IL-1β and TNF), and chemokines (CCL20, CXCL1, and CXCL2) that were associated to epithelial responses are also upregulated after the administration of the combination treatment in the post-flu superinfection model, suggesting that the epithelium is also an important flagellin-specific driving force in the lung damaged by viral and bacterial infections. abstract: Bacterial infections of the respiratory tract constitute a major cause of death worldwide. Given the constant rise in bacterial resistance to antibiotics, treatment failure is increasingly frequent. In this context, innovative therapeutic strategies are urgently needed. Stimulation of innate immune cells in the respiratory tract [via activation of Toll-like receptors (TLRs)] is an attractive approach for rapidly activating the body's immune defenses against a broad spectrum of microorganisms. Previous studies of the TLR5 agonist flagellin in animal models showed that standalone TLR stimulation does not result in the effective treatment of pneumococcal respiratory infection but does significantly improve the therapeutic outcome of concomitant antibiotic treatment. Here, we investigated the antibacterial interaction between antibiotic and intranasal flagellin in a mouse model of pneumococcal respiratory infection. Using various doses of orally administered amoxicillin or systemically administered cotrimoxazole, we found that the intranasal instillation of flagellin (a dose that promotes maximal lung pro-inflammatory responses) induces synergistic rather than additive antibacterial effects against antibiotic–susceptible pneumococcus. We next set up a model of infection with pneumococcus that is resistant to multiple antibiotics in the context of influenza superinfection. Remarkably, the combination of amoxicillin and flagellin effectively treated superinfection with the amoxicillin-resistant pneumococcus since the bacterial clearance was increased by more than 100-fold compared to standalone treatments. Our results also showed that, in response to flagellin, the lung tissue generated an innate immune response even though it had been damaged by the influenza virus and pneumococcal infections. In conclusion, we demonstrated that the selective boosting of lung innate immunity is a conceptually advantageous approach for improving the effectiveness of antibiotic treatment and fighting antibiotic-resistant bacteria. url: https://doi.org/10.3389/fimmu.2019.00723 doi: 10.3389/fimmu.2019.00723 id: cord-265855-zf52vl11 author: Mayor-Ibarguren, Ander title: A Hypothesis for the Possible Role of Zinc in the Immunological Pathways Related to COVID-19 Infection date: 2020-07-10 words: 5324.0 sentences: 283.0 pages: flesch: 47.0 cache: ./cache/cord-265855-zf52vl11.txt txt: ./txt/cord-265855-zf52vl11.txt summary: Zinc deficiency may increase ACE-2 receptor activity on type 2 pneumocytes and other cells that are infected by SARS-COV-2, mainly in the lower respiratory tract. Although there are no specific data regarding zinc in this pathway for SARS-CoV-2, zinc may limit infection through upregulation of IFN-alpha production and an increase in its antiviral activity (77, 78) . Thus, patients with IL-6-174 GG polymorphism (C-carriers) may be susceptible to developing a severe infection due to SARS-CoV-2, leading to an increase in IL-6 levels that produce a cytokine storm related to impaired zinc homeostasis. We believe there is enough evidence to further investigate how zinc status or homeostasis is involved in the pathogenesis of severe illness produced by SARS-CoV-2 infection, and its potential role as an active treatment should be assessed in clinical trials. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32754165/ doi: 10.3389/fimmu.2020.01736 id: cord-325129-faptufak author: Meini, Simone title: Understanding the Pathophysiology of COVID-19: Could the Contact System Be the Key? date: 2020-08-11 words: 5501.0 sentences: 255.0 pages: flesch: 38.0 cache: ./cache/cord-325129-faptufak.txt txt: ./txt/cord-325129-faptufak.txt summary: Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. In this review, we try to address the complex link between the pathophysiology of COVID-19 and the different proteolytic defense systems operating in human vasculature, investigating the role of the mediators involved and speculating on the possibility of pharmacological modulation. After binding through its B2R, BK activates signaling pathways resulting in increased vascular permeability, vasodilation, edema formation, hypotension, pain, fever (14) : all typical clinical features of COVID-19. (79) hypothesized that a kinin-dependent local lung angioedema via B1R and eventually B2R is an important feature of COVID-19 and proposed that blocking the B2R and inhibiting plasma KAL activity might be beneficial in early disease, preventing ARDS. abstract: To date the pathophysiology of COVID-19 remains unclear: this represents a factor determining the current lack of effective treatments. In this paper, we hypothesized a complex host response to SARS-CoV-2, with the Contact System (CS) playing a pivotal role in innate immune response. CS is linked with different proteolytic defense systems operating in human vasculature: the Kallikrein–Kinin (KKS), the Coagulation/Fibrinolysis and the Renin–Angiotensin (RAS) Systems. We investigated the role of the mediators involved. CS consists of Factor XII (FXII) and plasma prekallikrein (complexed to high-molecular-weight kininogen-HK). Autoactivation of FXII by contact with SARS-CoV-2 could lead to activation of intrinsic coagulation, with fibrin formation (microthrombosis), and fibrinolysis, resulting in increased D-dimer levels. Activation of kallikrein by activated FXII leads to production of bradykinin (BK) from HK. BK binds to B2-receptors, mediating vascular permeability, vasodilation and edema. B1-receptors, binding the metabolite [des-Arg(9)]-BK (DABK), are up-regulated during infections and mediate lung inflammatory responses. BK could play a relevant role in COVID-19 as already described for other viral models. Angiotensin-Converting-Enzyme (ACE) 2 displays lung protective effects: it inactivates DABK and converts Angiotensin II (Ang II) into Angiotensin-(1-7) and Angiotensin I into Angiotensin-(1-9). SARS-CoV-2 binds to ACE2 for cell entry, downregulating it: an impaired DABK inactivation could lead to an enhanced activity of B1-receptors, and the accumulation of Ang II, through a negative feedback loop, may result in decreased ACE activity, with consequent increase of BK. Therapies targeting the CS, the KKS and action of BK could be effective for the treatment of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32849666/ doi: 10.3389/fimmu.2020.02014 id: cord-304626-ffao7vka author: Mellors, Jack title: Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics date: 2020-07-09 words: 11744.0 sentences: 539.0 pages: flesch: 34.0 cache: ./cache/cord-304626-ffao7vka.txt txt: ./txt/cord-304626-ffao7vka.txt summary: A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. Infected host cells which present viral antigens on the cell surface membrane can activate the classical pathway, as the antigens bind IgM/IgG to induce complement dependent cytotoxicity (CDC). Non-neutralizing antibodies can still bind the viral target with the potential to cross-link with Fc receptors, or activate complement and interact with complement receptors, to enhance viral infection of host cells (241) . Use of the non-neutralizing influenza virus M2 extracellular vaccine in mice required functional C3 to confer protection and induce effective humoral and cell-mediated immune responses (245) . abstract: The complement system is a key component of innate immunity which readily responds to invading microorganisms. Activation of the complement system typically occurs via three main pathways and can induce various antimicrobial effects, including: neutralization of pathogens, regulation of inflammatory responses, promotion of chemotaxis, and enhancement of the adaptive immune response. These can be vital host responses to protect against acute, chronic, and recurrent viral infections. Consequently, many viruses (including dengue virus, West Nile virus and Nipah virus) have evolved mechanisms for evasion or dysregulation of the complement system to enhance viral infectivity and even exacerbate disease symptoms. The complement system has multifaceted roles in both innate and adaptive immunity, with both intracellular and extracellular functions, that can be relevant to all stages of viral infection. A better understanding of this virus-host interplay and its contribution to pathogenesis has previously led to: the identification of genetic factors which influence viral infection and disease outcome, the development of novel antivirals, and the production of safer, more effective vaccines. This review will discuss the antiviral effects of the complement system against numerous viruses, the mechanisms employed by these viruses to then evade or manipulate this system, and how these interactions have informed vaccine/therapeutic development. Where relevant, conflicting findings and current research gaps are highlighted to aid future developments in virology and immunology, with potential applications to the current COVID-19 pandemic. url: https://doi.org/10.3389/fimmu.2020.01450 doi: 10.3389/fimmu.2020.01450 id: cord-333670-qv1orlv5 author: Mutti, Luciano title: Coronavirus Disease (Covid-19): What Are We Learning in a Country With High Mortality Rate? date: 2020-05-28 words: 2500.0 sentences: 123.0 pages: flesch: 40.0 cache: ./cache/cord-333670-qv1orlv5.txt txt: ./txt/cord-333670-qv1orlv5.txt summary: In Italy, the possibility of performing autopsies or post-mortem diagnostic studies on suspect, probable, or confirmed COVID-19 cases has been intensively debated (5, 6) ; however, postmortem pathological analysis of COVID-19 patients in China has shown findings consistent with Acute Respiratory Distress Syndrome (ARDS) (7-9) (Figure 1 ). Consistently, recent results indicate that a systemic immune dysregulation that triggers auto-sustaining inflammatory lung damage, causing fatal respiratory-failure and consequent multiorgan-failure, is the main virus-related-death cause in patients who develop SARS-CoV-2 (10). Overall, understanding the role of pro-inflammatory cytokines certainly unravels a new battleground against the lethal clinical effect of CODIV-19 infection; this, along with the identification of a high-risk autoimmune profile, including the genotyping of Class I and II HLA, which have a key role in shaping the anti-viral immune response and Th1/Th2 lymphocyte subset response (Figure 1) , and immune-profiling, could also help to prevent these dangerous evolutions of the disease (29) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32574270/ doi: 10.3389/fimmu.2020.01208 id: cord-293736-nyvwv31m author: Méry, Geoffroy title: COVID-19: Underlying Adipokine Storm and Angiotensin 1-7 Umbrella date: 2020-07-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus leading to a global health outbreak. Despite the high mortality rates from SARS-CoV-1 and Middle-East respiratory syndrome (MERS)-CoV infections, which both sparked the interest of the scientific community, the underlying physiopathology of the SARS-CoV-2 infection, remains partially unclear. SARS-CoV-2 shares similar features with SARS-CoV-1, notably the use of the angiotensin conversion enzyme 2 (ACE2) as a receptor to enter the host cells. However, some features of the SARS-CoV-2 pandemic are unique. In this work, we focus on the association between obesity, metabolic syndrome, and type 2 diabetes on the one hand, and the severity of COVID-19 infection on the other, as it seems greater in these patients. We discuss how adipocyte dysfunction leads to a specific immune environment that predisposes obese patients to respiratory failure during COVID-19. We also hypothesize that an ACE2-cleaved protein, angiotensin 1-7, has a beneficial action on immune deregulation and that its low expression during the SARS-CoV-2 infection could explain the severity of infection. This introduces angiotensin 1-7 as a potential candidate of interest in therapeutic research on CoV infections. url: https://www.ncbi.nlm.nih.gov/pubmed/32793244/ doi: 10.3389/fimmu.2020.01714 id: cord-340741-bhxm4zua author: Nayak, Tapas Kumar title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages date: 2019-04-12 words: 8025.0 sentences: 394.0 pages: flesch: 48.0 cache: ./cache/cord-340741-bhxm4zua.txt txt: ./txt/cord-340741-bhxm4zua.txt summary: title: P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. In summary, for the first time it has been shown that CHIKV triggers robust TNF production (a key mediator of CHIKV induced inflammation) in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and viral protein nsP2 interacts with both the MAPKs during infection. abstract: Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future. url: https://doi.org/10.3389/fimmu.2019.00786 doi: 10.3389/fimmu.2019.00786 id: cord-348283-7xorq5ce author: Naz, Anam title: Designing Multi-Epitope Vaccines to Combat Emerging Coronavirus Disease 2019 (COVID-19) by Employing Immuno-Informatics Approach date: 2020-07-10 words: 8183.0 sentences: 482.0 pages: flesch: 56.0 cache: ./cache/cord-348283-7xorq5ce.txt txt: ./txt/cord-348283-7xorq5ce.txt summary: The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Designed vaccines were then tested with different epitopes, including Truncated Ov-ASP-1 Protein (residues 10-153) and Beta defensin (45 residues long), and constructs having higher antigenicity and that are predicted to produce high antibody titers were added with the multi epitope vaccine construct to the enhance immune response (30) . For the interaction analysis of vaccine 3 and BCR (CD79), the HADDOCK server clustered 140 probable structures into 13 different clusters, which represented a total of 70% of the water-refined models. abstract: A recent pandemic caused by a single-stranded RNA virus, COVID-19, initially discovered in China, is now spreading globally. This poses a serious threat that needs to be addressed immediately. Genome analysis of SARS-CoV-2 has revealed its close relation to SARS-coronavirus along with few changes in its spike protein. The spike protein aids in receptor binding and viral entry within the host and therefore represents a potential target for vaccine and therapeutic development. In the current study, the spike protein of SARS-CoV-2 was explored for potential immunogenic epitopes to design multi-epitope vaccine constructs. The S1 and S2 domains of spike proteins were analyzed, and two vaccine constructs were prioritized with T-cell and B-cell epitopes. We adapted a comprehensive predictive framework to provide novel insights into immunogenic epitopes of spike proteins, which can further be evaluated as potential vaccine candidates against COVID-19. Prioritized epitopes were then modeled using linkers and adjuvants, and respective 3D models were constructed to evaluate their physiochemical properties and their possible interactions with ACE2, HLA Superfamily alleles, TLR2, and TLR4. url: https://www.ncbi.nlm.nih.gov/pubmed/32754160/ doi: 10.3389/fimmu.2020.01663 id: cord-256998-or73in8m author: Nguyen, Khue G. title: Localized Interleukin-12 for Cancer Immunotherapy date: 2020-10-15 words: 26912.0 sentences: 1416.0 pages: flesch: 37.0 cache: ./cache/cord-256998-or73in8m.txt txt: ./txt/cord-256998-or73in8m.txt summary: Among the more notable responses in other early preclinical studies, nearly half of mice bearing established B16F10 melanomas experienced complete tumor regression following 2 weekly treatments with pIL-12+EP (124) . In preclinical studies, a single intratumoral injection of mRNA encoding murine IL-12 (mIL-12) increased IFNγ expression and genes associated with a Th1 response in MC38 tumor-bearing mice (190) . In a useful comparison against other cytokines, one study demonstrated that Ad-IFN-γ had no greater antitumor activity than an empty Ad vector, whereas AdmIL-12 induced complete regressions of P815 mastocytomas in >80% of treated mice (219) . Antitumor activity on xenografts of human lung tissues indicated that liposomal encapsulation is a promising approach capable of eliminating tumor cells and inducing lymphocyte infiltration 2 weeks after i.t. injection. Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8 + T-cell immunity and NK activity abstract: Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990's showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12's pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest. Diverse IL-12 delivery systems, from immunocytokine fusions to polymeric nanoparticles, have demonstrated robust antitumor immunity with reduced adverse events in preclinical studies. Several localized IL-12 delivery approaches have recently reached the clinical stage with several more at the precipice of translation. Taken together, localized delivery systems are supporting an IL-12 renaissance which may finally allow this potent cytokine to fulfill its considerable clinical potential. This review begins with a brief historical account of cytokine monotherapies and describes how IL-12 went from promising new cure to ostracized black sheep following multiple on-study deaths. The bulk of this comprehensive review focuses on developments in diverse localized delivery strategies for IL-12-based cancer immunotherapies. Advantages and limitations of different delivery technologies are highlighted. Finally, perspectives on how IL-12-based immunotherapies may be utilized for widespread clinical application in the very near future are offered. url: https://www.ncbi.nlm.nih.gov/pubmed/33178203/ doi: 10.3389/fimmu.2020.575597 id: cord-328549-r56lih8j author: Okamoto, Masaaki title: Regulation of RIG-I Activation by K63-Linked Polyubiquitination date: 2018-01-05 words: 3618.0 sentences: 216.0 pages: flesch: 47.0 cache: ./cache/cord-328549-r56lih8j.txt txt: ./txt/cord-328549-r56lih8j.txt summary: First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. However, recent studies have reported three other ubiquitin ligases, RING finger protein leading to RIG-I activation (Riplet), mex-3 RNA-binding family member C (MEX3C), and TRIM4, which are required for the polyubiquitination and activation of RIG-I (28-30). abstract: RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double-stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of the innate immune responses. The protein comprises N-terminal two caspase activation and recruitment domains (2CARDs), an RNA helicase domain, and the C-terminal domain (CTD). The CTD recognizes 5′-triphosphate viral dsRNA. After recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs assemble and make a core that promotes the aggregation of the mitochondrial antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then triggers the signal to induce the innate immune responses. However, subsequent studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates the CTD. The physiological significance of each ubiquitin ligases has been shown by knockout and knockdown studies, but there appears to be contradictory to evidence reported in the literature. In this review, we summarize recent findings related to K63-linked polyubiquitination and propose a model that could reconcile current contradictory theories. We also discuss the physiological significance of the ubiquitin ligases in the immune system against viral infection. url: https://www.ncbi.nlm.nih.gov/pubmed/29354136/ doi: 10.3389/fimmu.2017.01942 id: cord-001674-tp4o7fxx author: Oliveira, Cláudia C. title: Alternative Antigen Processing for MHC Class I: Multiple Roads Lead to Rome date: 2015-06-05 words: 6630.0 sentences: 347.0 pages: flesch: 46.0 cache: ./cache/cord-001674-tp4o7fxx.txt txt: ./txt/cord-001674-tp4o7fxx.txt summary: An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. This intramembrane proteolysis by SPP is thought to be important for the clearance of the ER membrane by removing small protein remnants anchored at FIGURE 1 | Classical and alternative pathways for MHC class I presentation. Furin-processed antigens targeted to the secretory route were presented by MHC class I at the cell surface and could elicit functional CD8 T-cell responses in vivo in a TAP-independent fashion (75, 81) . Autophagy mediates transporter associated with antigen processing-independent presentation of viral epitopes through MHC class I pathway A transporter associated with antigen-processing independent vacuolar pathway for the MHC class I-mediated presentation of endogenous transmembrane proteins abstract: The well described conventional antigen-processing pathway is accountable for most peptides that end up in MHC class I molecules at the cell surface. These peptides experienced liberation by the proteasome and transport by the peptide transporter TAP. However, there are multiple roads that lead to Rome, illustrated by the increasing number of alternative processing pathways that have been reported during last years. Interestingly, TAP-deficient individuals do not succumb to viral infections, suggesting that CD8 T cell immunity is sufficiently supported by alternative TAP-independent processing pathways. To date, a diversity of viral and endogenous TAP-independent peptides have been identified in the grooves of different MHC class I alleles. Some of these peptides are not displayed by normal TAP-positive cells and we therefore called them TEIPP, for “T-cell epitopes associated with impaired peptide processing.” TEIPPs are hidden self-antigens, are derived from normal housekeeping proteins, and are processed via unconventional processing pathways. Per definition, TEIPPs are presented via TAP-independent pathways, but recent data suggest that part of this repertoire still depend on proteasome and metalloprotease activity. An exception is the C-terminal peptide of the endoplasmic reticulum (ER)-membrane-spanning ceramide synthase Trh4 that is surprisingly liberated by the signal peptide peptidase (SPP), the proteolytic enzyme involved in cleaving leader sequences. The intramembrane cleaving SPP is thereby an important contributor of TAP-independent peptides. Its family members, like the Alzheimer’s related presenilins, might contribute as well, according to our preliminary data. Finally, alternative peptide routing is an emerging field and includes processes like the unfolded protein response, the ER-associated degradation, and autophagy-associated vesicular pathways. These data convince us that there is a world to be discovered in the field of unconventional antigen processing. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457021/ doi: 10.3389/fimmu.2015.00298 id: cord-253108-p3wlw5d4 author: Olson, Brian M. title: Interleukin 35: A Key Mediator of Suppression and the Propagation of Infectious Tolerance date: 2013-10-18 words: 7447.0 sentences: 260.0 pages: flesch: 36.0 cache: ./cache/cord-253108-p3wlw5d4.txt txt: ./txt/cord-253108-p3wlw5d4.txt summary: Following more than a decade of studies aimed at elucidating the mechanisms that mediate Treg activity, interest was rekindled in the mid-1990s with the transformational research of Sakaguchi and colleagues, who specifically identified a population of CD4+CD25+ T cells that had suppressive function, which were coined as naturally occurring thymic-derived Tregs, or natural Abbreviations: APC, antigen-presenting cell; DC, dendritic cell; EAE, experimental autoimmune encephalitis; Ebi3, Epstein-Barr virus-induced gene 3; IL, interleukin; iTreg, induced regulatory T cell; NIMA, non-inherited maternal antigen; NK, natural killer; nTreg, natural regulatory T cell; PAP, prostatic acid phosphatase; TGF, transforming growth factor; Treg, regulatory T cell. When activated in these conditions, iTregs gain potent suppressive functions, inhibiting T-cell proliferation and effector functions in an antigen non-specific fashion, and play a central role in mediating regulation and propagating infectious tolerance in a variety of malignancies, including infectious diseases and cancer. abstract: The importance of regulatory T cells (Tregs) in balancing the effector arm of the immune system is well documented, playing a central role in preventing autoimmunity, facilitating graft tolerance following organ transplantation, and having a detrimental impact on the development of anti-tumor immunity. These regulatory responses use a variety of mechanisms to mediate suppression, including soluble factors. While IL-10 and TGF-β are the most commonly studied immunosuppressive cytokines, the recently identified IL-35 has been shown to have potent suppressive function in vitro and in vivo. Furthermore, not only does IL-35 have the ability to directly suppress effector T cell responses, it is also able to expand regulatory responses by propagating infectious tolerance and generating a potent population of IL-35-expressing inducible Tregs. In this review, we summarize research characterizing the structure and function of IL-35, examine its role in disease, and discuss how it can contribute to the induction of a distinct population of inducible Tregs. url: https://doi.org/10.3389/fimmu.2013.00315 doi: 10.3389/fimmu.2013.00315 id: cord-323590-m4jsu1q5 author: Ortiz de Landazuri, Iñaki title: Manufacturing and Management of CAR T-Cell Therapy in “COVID-19’s Time”: Central Versus Point of Care Proposals date: 2020-10-15 words: 4339.0 sentences: 230.0 pages: flesch: 41.0 cache: ./cache/cord-323590-m4jsu1q5.txt txt: ./txt/cord-323590-m4jsu1q5.txt summary: The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. Therefore, the aim of this mini-review is to focus on how the effects caused by the pandemic have affected this therapy taking into consideration the differences between the large-scale centralized production of CAR T-cells by the pharmaceutical industry versus the product manufacturing processes employed by the academic/hospital environment. We also review different aspects of CAR T-cell therapy, including patient selection and resource prioritization performed in our center during the COVID-19 pandemic. abstract: The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has generated a significant repercussion on the administration of adoptive cell therapies, including chimeric antigen receptor (CAR) T-cells. The closing of borders, the reduction of people transit and the confinement of the population has affected the supply chains of these life-saving medical products. The aim of this mini-review is to focus on how the COVID-19 pandemic has affected CAR T-cell therapy and taking into consideration the differences between the large-scale centralized productions for the pharmaceutical industry versus product manufacturing in the academic/hospital environment. We also review different aspects of CAR T-cell therapy and our managerial experience of patient selection, resource prioritization and some practical aspects to consider for safe administration. Although hospitals have been forced to change their usual workflows to cope with the saturation of health services by hospitalized patients, we recommend centers to continue offering this potentially curative treatment for patients with relapsed/refractory hematologic malignancies. Consequently, we propose appropriate selection criteria, early intervention to attenuate neurotoxicity or cytokine release syndrome with tocilizumab and prophylactic/preventive strategies to prevent infection. These considerations may apply to other emerging adoptive cell treatments and the corresponding manufacturing processes. url: https://doi.org/10.3389/fimmu.2020.573179 doi: 10.3389/fimmu.2020.573179 id: cord-333041-69n2wwn3 author: Pal, Anandita title: Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection date: 2020-08-11 words: 4394.0 sentences: 227.0 pages: flesch: 43.0 cache: ./cache/cord-333041-69n2wwn3.txt txt: ./txt/cord-333041-69n2wwn3.txt summary: Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Obesity is an independent risk factor for increased morbidity and mortality upon infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic. The SPM precursor 17-hydroxydocosahexaenoic acid (17-HDHA) increased antibody levels and improved survival upon pH1N1 influenza vaccination and infection in lean mice by promoting B cell differentiation toward the formation of CD138 + long-lived antibody secreting cells (18) . Taken together, these data suggest that the susceptibility of obese individuals to environmental lung diseases may drive an altered pulmonary immune response and a state of SPM deficiency that increases the morbidity and mortality to respiratory infections, including COVID-19. abstract: Obesity is a major independent risk factor for increased morbidity and mortality upon infection with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), which is responsible for the current coronavirus disease pandemic (COVID-19). Therefore, there is a critical need to identify underlying metabolic factors associated with obesity that could be contributing toward increased susceptibility to SARS-CoV-2 in this vulnerable population. Here, we focus on the critical role of potent endogenous lipid metabolites known as specialized pro-resolving mediators (SPMs) that are synthesized from polyunsaturated fatty acids. SPMs are generated during the transition of inflammation to resolution and have a vital role in directing damaged tissues to homeostasis; furthermore, SPMs display anti-viral activity in the context of influenza infection without being immunosuppressive. We cover evidence from rodent and human studies to show that obesity, and its co-morbidities, induce a signature of SPM deficiency across immunometabolic tissues. We further discuss how the effects of obesity upon SARS-CoV-2 infection are likely exacerbated with environmental exposures that promote chronic pulmonary inflammation and augment SPM deficits. Finally, we highlight potential approaches to overcome the loss of SPMs using dietary and pharmacological interventions. Collectively, this mini-review underscores the need for mechanistic studies on how SPM deficiencies driven by obesity and environmental exposures may exacerbate the response to SARS-CoV-2. url: https://doi.org/10.3389/fimmu.2020.01997 doi: 10.3389/fimmu.2020.01997 id: cord-268501-z4oztgi0 author: Palatnik-de-Sousa, Clarisa B. title: What Would Jenner and Pasteur Have Done About COVID-19 Coronavirus? The Urges of a Vaccinologist date: 2020-08-26 words: 6331.0 sentences: 280.0 pages: flesch: 46.0 cache: ./cache/cord-268501-z4oztgi0.txt txt: ./txt/cord-268501-z4oztgi0.txt summary: In fact, by May 11th, 2020 seven vaccines had already entered Phase I clinical trials: (1) encapsulated mRNA encoding protein S (Moderna and NIAID, USA); (2) Adenovirus expressing protein S (Cansino Biologics, China); (3) DCs modified with lentivirus expressing several proteins and CTLs (Shenzen Geno-Immune Medical, China); (4) an APC modified with lentivirus expressing several viral proteins (35); (5) Inno 4800, SARS CoV2 DNA Injection (Innovio, USA); (6) ChAdOx1 vaccine from the Jenner Institute, Oxford University, (UK) which is a genetically modified Adenovirus expressing Coronavirus proteins (39) , and is also being tested in a Phase II trial; and finally (7) the whole inactivated coronavirus with Alum by Sinovac, China (40) . Furthermore, in vaccinated monkeys, seven days after infection, the Sinovac inactivated vaccine at 6 µg/dose induced high titers of IgG antibodies directed against the S, RBD and lower levels of anti-N protein antibodies, high titers of virus neutralizing antibodies with no detected antibodydependent enhancement of disease (ADE) (40) . abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32983183/ doi: 10.3389/fimmu.2020.02173 id: cord-004151-9815ikzg author: Pan, Xiaocheng title: Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) date: 2020-01-08 words: 6365.0 sentences: 371.0 pages: flesch: 56.0 cache: ./cache/cord-004151-9815ikzg.txt txt: ./txt/cord-004151-9815ikzg.txt summary: To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. In an attempt to identify anti-PRRSV CTL epitopes in this study, first, predicted peptide epitopes derived from PRRSV were synthesized, and a trimolecular complex, the structure of the epitope from PRRSV-NSP9 (TMPPGFELY, termed NSP9-TMP9)-bound SLA-1 * 1502 (pSLA-1 * 1502), was solved. The purified complex (44 kDa) of pSLA-1 * 1502 with the NSP9-TMP9 peptide (amino acid sequence TMPPGFELY, derived from residues 198-206 of the PRRSV non-structural protein) was dialyzed against crystallization buffer (20 mM Tris-HCl pH 8.0, 50 mM NaCl) and concentrated to 12 mg/mL. abstract: To investigate CTL epitope applications in swine, SLA-1(*)1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1(*)1502 (pSLA-1(*)1502) complexes, and the crystal structure of the SLA-1(*)1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1(*)1502 is different from that of the peptides presented by the known pSLA-1(*)0401 and pSLA-3(*)hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1(*)1502 is unique and is important for peptide binding. Next, the potential SLA-1(*)1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1(*)1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1(*)1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1(*)1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960135/ doi: 10.3389/fimmu.2019.02995 id: cord-262944-9k64f0tw author: Parker, Elaine L. title: Viral-Immune Cell Interactions at the Maternal-Fetal Interface in Human Pregnancy date: 2020-10-07 words: 9814.0 sentences: 497.0 pages: flesch: 43.0 cache: ./cache/cord-262944-9k64f0tw.txt txt: ./txt/cord-262944-9k64f0tw.txt summary: In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. We will focus on the viruses human Cytomegalovirus (HCMV) and ZIKV, which are known causes of adverse pregnancy outcomes and delve into how they interact with various decidual immune cells to promote their survival and replication. We will explore further the role that NK cells play in specific viral infections in pregnancy TORCH PATHOGENS HCMV Human cytomegalovirus (HCMV) was first described in 1954 by Margaret Smith, who replicated a virus from two newborn babies who had died from cytomegalic inclusion disease (CID) (41) . A study performed using decidual and chorionic villous tissue from early and mid-gestation human pregnancy shows that ZIKV appears to elevate type I and III IFN expression, which does not occur in HCMV infection (131) . abstract: The human decidua and placenta form a distinct environment distinguished for its promotion of immunotolerance to infiltrating semiallogeneic trophoblast cells to enable successful pregnancy. The maternal-fetal interface also successfully precludes transmission of most pathogens. This barrier function occurs in conjunction with a diverse influx of decidual immune cells including natural killer cells, macrophages and T cells. However, several viruses, among other microorganisms, manage to escape destruction by the host adaptive and innate immune system, leading to congenital infection and adverse pregnancy outcomes. In this review, we describe mechanisms of pathogenicity of two such viral pathogens, Human cytomegalovirus (HCMV) and Zika virus (ZIKV) at the maternal-fetal interface. Host decidual immune cell responses to these specific pathogens will be considered, along with their interactions with other cell types and the ways in which these immune cells may both facilitate and limit infection at different stages of pregnancy. Neither HCMV nor ZIKV naturally infect commonly used animal models [e.g., mice] which makes it challenging to understand disease pathogenesis. Here, we will highlight new approaches using placenta-on-a-chip and organoids models that are providing functional and physiologically relevant ways to study viral-host interaction at the maternal-fetal interface. url: https://www.ncbi.nlm.nih.gov/pubmed/33117336/ doi: 10.3389/fimmu.2020.522047 id: cord-026866-0hlre9i6 author: Perruzza, Lisa title: Prophylactic Activity of Orally Administered FliD-Reactive Monoclonal SIgA Against Campylobacter Infection date: 2020-06-09 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Campylobacter infection is one of the most common causes of bacterial gastroenteritis worldwide and a major global health threat due to the rapid development of antibiotic resistance. Currently, there are no vaccines approved to prevent campylobacteriosis, and rehydration is the main form of therapy. Secretory immunoglobulin A (SIgA) is the main antibody class found in mucous secretions, including human milk, and serves as the first line of defense for the gastrointestinal epithelium against enteric pathogens. In this study, we describe the prophylactic activity of orally delivered recombinant SIgA generated from two human monoclonal antibodies (CAA1 and CCG4) isolated for their reactivity against the flagellar-capping protein FliD, which is essential for bacteria motility and highly conserved across Campylobacter species associated with severe enteritis. In an immunocompetent weaned mouse model, a single oral administration of FliD-reactive SIgA CAA1 or CCG4 at 2 h before infection significantly enhances Campylobacter clearance at early stages post-infection, reducing the levels of inflammation markers associated with epithelial damage and polymorphonuclear (PMN) cells infiltration in the cecum lamina propria. Our data indicate that the prophylactic activity of CAA1 and CCG4 is not only dependent on the specificity to FliD but also on the use of the SIgA format, as the immunoglobulin G (IgG) versions of the same antibodies did not confer a comparable protective effect. Our work emphasizes the potential of FliD as a target for the development of vaccines and supports the concept that orally administered FliD-reactive SIgA can be developed to prevent or mitigate the severity of Campylobacter infections as well as the development of post-infection syndromes. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7296071/ doi: 10.3389/fimmu.2020.01011 id: cord-344093-3bniy5b5 author: Peteranderl, Christin title: The Impact of the Interferon/TNF-Related Apoptosis-Inducing Ligand Signaling Axis on Disease Progression in Respiratory Viral Infection and Beyond date: 2017-03-22 words: 12546.0 sentences: 578.0 pages: flesch: 34.0 cache: ./cache/cord-344093-3bniy5b5.txt txt: ./txt/cord-344093-3bniy5b5.txt summary: A prominent regulator of disease outcome, especially in-but not limited to-respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. (73) Cell death induction, e.g., Bcl-2-associated X protein, caspase-8, Fas-associated protein with death domain, Fas ligand, and TNF-related apoptosis-inducing ligand (TRAIL) dsRNA, polyI:C (4, 110) IAV (4, 5, 10, 115) Sendai virus (110) TRAIL Virus control by apoptosis induction in infected cells IAV (6, 170, 171) Tissue injury by apoptosis of both infected and non-infected alveolar epithelial cells, lung macrophages IAV (5, 7, 10) RSV (137) Necrosis of fibroblasts, dendritic cells, and epithelial cells IAV (146, 147, 168) Increased cellular infiltration CoV (175) Decreased expression of Na,K-ATPase, impaired epithelial fluid reabsorption IAV (11) iNTRODUCTiON In 1957, Isaacs and Lindenmann (1) first recognized the potential of a soluble and probably cell-derived factor to combat influenza virus infection and named this factor interferon [(IFN) from latin interferre, to interfere]. abstract: Interferons (IFNs) are well described to be rapidly induced upon pathogen-associated pattern recognition. After binding to their respective IFN receptors and activation of the cellular JAK/signal transducer and activator of transcription signaling cascade, they stimulate the transcription of a plethora of IFN-stimulated genes (ISGs) in infected as well as bystander cells such as the non-infected epithelium and cells of the immune system. ISGs may directly act on the invading pathogen or can either positively or negatively regulate the innate and adaptive immune response. However, IFNs and ISGs do not only play a key role in the limitation of pathogen spread but have also been recently found to provoke an unbalanced, overshooting inflammatory response causing tissue injury and hampering repair processes. A prominent regulator of disease outcome, especially in—but not limited to—respiratory viral infection, is the IFN-dependent mediator TRAIL (TNF-related apoptosis-inducing ligand) produced by several cell types including immune cells such as macrophages or T cells. First described as an apoptosis-inducing agent in transformed cells, it is now also well established to rapidly evoke cellular stress pathways in epithelial cells, finally leading to caspase-dependent or -independent cell death. Hereby, pathogen spread is limited; however in some cases, also the surrounding tissue is severely harmed, thus augmenting disease severity. Interestingly, the lack of a strictly controlled and well balanced IFN/TRAIL signaling response has not only been implicated in viral infection but might furthermore be an important determinant of disease progression in bacterial superinfections and in chronic respiratory illness. Conclusively, the IFN/TRAIL signaling axis is subjected to a complex modulation and might be exploited for the evaluation of new therapeutic concepts aiming at attenuation of tissue injury. url: https://doi.org/10.3389/fimmu.2017.00313 doi: 10.3389/fimmu.2017.00313 id: cord-032953-qy4b2l2f author: Picard-Sánchez, Amparo title: Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire date: 2020-09-11 words: 8218.0 sentences: 410.0 pages: flesch: 48.0 cache: ./cache/cord-032953-qy4b2l2f.txt txt: ./txt/cord-032953-qy4b2l2f.txt summary: title: Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire The results showed that, fish injected with parasite-specific antibodies (spAbs) became infected with the parasite, but showed lower disease signs and intensity of infection than the other groups, indicating a later establishment of the parasite. 1 https://www.genome.jp/tools-bin/clustalw To study the IgM and IgT repertoire in the fish used as serum donors for passive immunization, cDNA from anterior intestine of SUR and NAI donor fish were used as template in PCR amplifications for each primer combination (F + R). Thus, we studied the IgM and IgT repertoire in the GSB that acted as SUR and NAI serum donors for the passive immunization trial. The repertoire analysis was performed on the anterior intestine, as previous studies revealed that in this particular organ IgM and IgT transcript expression increased upon re-exposure to the parasite in resistant fish (29) . abstract: Passive immunization constitutes an emerging field of interest in aquaculture, particularly with the restrictions for antibiotic use. Enteromyxum leei is a myxozoan intestinal parasite that invades the paracellular space of the intestinal epithelium, producing a slow-progressing disease, leading to anorexia, cachexia and mortalities. We have previously demonstrated that gilthead sea bream (GSB, Sparus aurata) that survive E. leei infection become resistant upon re-exposure, and this resistance is directly related to the presence of high levels of specific IgM in serum. Thus, the current work was aimed to determine if passive immunization could help to prevent enteromyxosis in GSB and to study in detail the nature of these protective antibodies. Serum from a pool of resistant (SUR) or naïve (NAI) animals was intracoelomically injected 24 h prior to the E. leei-effluent challenge and at 9 days post-challenge (dpc). Effluent challenge lasted for 23 days, and then the injected groups were allocated in separate tanks with clean water. A non-lethal parasite diagnosis was performed at 56 dpc. At the final sampling (100 dpc), blood, serum and tissues were collected for histology, molecular diagnosis and the detection of circulating antibodies. In parallel, we performed an immunoglobulin repertoire analysis of the fish generating SUR and NAI sera. The results showed that, fish injected with parasite-specific antibodies (spAbs) became infected with the parasite, but showed lower disease signs and intensity of infection than the other groups, indicating a later establishment of the parasite. Repertoire analysis revealed that E. leei induced a polyclonal expansion of diverse IgM and IgT subsets that could be in part an evasion strategy of the parasite. Nonetheless, GSB was able to produce sufficient levels of parasite-spAbs to avoid re-infection of surviving animals and confer certain degree of protection upon passive transfer of antibodies. These results highlight the crucial role of spAb responses against E. leei and set the basis for the development of effective treatment or prophylactic methods for aquaculture. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516018/ doi: 10.3389/fimmu.2020.581361 id: cord-268781-6l74rrlm author: Poh, Chek Meng title: Multiplex Screening Assay for Identifying Cytotoxic CD8(+) T Cell Epitopes date: 2020-03-11 words: 6116.0 sentences: 312.0 pages: flesch: 50.0 cache: ./cache/cord-268781-6l74rrlm.txt txt: ./txt/cord-268781-6l74rrlm.txt summary: Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8 + T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8 + T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Splenocytes from vaccinated mice challenged by a lethal PR8 infection were used to measure epitope-specific CD8 T cell effector functions through direct (in vivo cytotoxicity) and indirect (IFNγ-ICS) assays. abstract: The cytotoxicity of epitope-specific CD8(+) T cells is usually measured indirectly through IFNγ production. Existing assays that directly measure this activity are limited mainly to measurements of up to two specificities in a single reaction. Here, we develop a multiplex cytotoxicity assay that allows direct, simultaneous measurement of up to 23 different specificities of CD8(+) T cells in a single reaction. This can greatly reduce the amount of starting clinical materials for a systematic screening of CD8(+) T cell epitopes. In addition, this greatly enhanced capacity enables the incorporation of irrelevant epitopes for determining the non-specific killing activity of CD8(+) T cells, thereby allowing to measure the actual epitope-specific cytotoxicity activities. This technique is shown to be useful to study both human and mouse CD8(+) T cells. Besides, our results from human PBMCs and three independent infectious animal models (MERS, influenza and malaria) further reveal that IFNγ expression by epitope-specific CD8(+) T cells does not always correlate with their cell-killing potential, highlighting the need for using cytotoxicity assays in specific contexts (e.g., evaluating vaccine candidates). Overall, our approach opens up new possibilities for comprehensive analyses of CD8(+) T cell cytotoxicity in a practical manner. url: https://doi.org/10.3389/fimmu.2020.00400 doi: 10.3389/fimmu.2020.00400 id: cord-267567-w39f584z author: Pombo, Joao Palma title: Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections date: 2018-06-04 words: 4034.0 sentences: 217.0 pages: flesch: 32.0 cache: ./cache/cord-267567-w39f584z.txt txt: ./txt/cord-267567-w39f584z.txt summary: Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests counter strategies employed by host cells, which actively modulate several of these networks in response to infection, enhancing interferon signaling by doing so, and thus creating an antiviral environment. In this review, we discuss recent data on mechanisms of alteration of lipid metabolic pathways during infection by flaviviruses, with a focus on cholesterol and fatty acid biosynthesis, which can be manipulated by the invading viruses to support replication, but can also be modulated by the host immune system itself, as a means to fight infection. abstract: Cellular lipid homeostasis is maintained through an intricately linked array of anabolic and catabolic pathways. Upon flavivirus infections, these are significantly altered: on the one hand, these viruses can co-opt lipid metabolic pathways to generate ATP to facilitate replication, or to synthesize membrane components to generate replication sites; on the other hand, more recent evidence suggests counter strategies employed by host cells, which actively modulate several of these networks in response to infection, enhancing interferon signaling by doing so, and thus creating an antiviral environment. In this review, we discuss recent data on mechanisms of alteration of lipid metabolic pathways during infection by flaviviruses, with a focus on cholesterol and fatty acid biosynthesis, which can be manipulated by the invading viruses to support replication, but can also be modulated by the host immune system itself, as a means to fight infection. url: https://doi.org/10.3389/fimmu.2018.01276 doi: 10.3389/fimmu.2018.01276 id: cord-284409-xiyeceib author: Prabakaran, Ponraj title: The Antibody Germline/Maturation Hypothesis, Elicitation of Broadly Neutralizing Antibodies Against HIV-1 and Cord Blood IgM Repertoires date: 2014-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We have previously observed that all known potent broadly neutralizing antibodies (bnAbs) against HIV-1 are highly divergent from their putative germline predecessors in contrast to bnAbs against viruses causing acute infections such as henipaviruses and SARS CoV, which are much less divergent from their germline counterparts. Consequently, we have hypothesized that germline antibodies may not bind to the HIV-1 envelope glycoprotein (Env) because they are so different compared to the highly somatically mutated HIV-1-specific bnAbs. We have further hypothesized that the immunogenicity of highly conserved epitopes on the HIV-1 envelope glycoproteins (Envs) may be reduced or eliminated by their very weak or absent interactions with germline antibodies and immune responses leading to the elicitation of bnAbs may not be initiated and/or sustained. Even if such responses are initiated, the maturation pathways are so extraordinarily complex that prolonged periods of time may be required for elicitation of bnAbs with defined unique sequences. We provided the initial evidence supporting this antibody germline/maturation hypothesis, which prompted a number of studies to design vaccine immunogens that could bind putative germline predecessors of known bnAbs and to explore complex B cell lineages. However, guiding the immune system through the exceptionally complex antibody maturation pathways to elicit known bnAbs remains a major challenge. Here, we discuss studies exploring the antibody germline/maturation hypothesis as related to elicitation of bnAbs against HIV-1 and present our recent data demonstrating the existence of germline-like precursors of VRC01 antibodies in a human cord blood IgM library. url: https://doi.org/10.3389/fimmu.2014.00398 doi: 10.3389/fimmu.2014.00398 id: cord-343824-00mqmpzw author: Qian, Wei title: The C-Terminal Effector Domain of Non-Structural Protein 1 of Influenza A Virus Blocks IFN-β Production by Targeting TNF Receptor-Associated Factor 3 date: 2017-07-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Influenza A virus non-structural protein 1 (NS1) antagonizes interferon response through diverse strategies, particularly by inhibiting the activation of interferon regulatory factor 3 (IRF3) and IFN-β transcription. However, the underlying mechanisms used by the NS1 C-terminal effector domain (ED) to inhibit the activation of IFN-β pathway are not well understood. In this study, we used influenza virus subtype of H5N1 to demonstrate that the NS1 C-terminal ED but not the N-terminal RNA-binding domain, binds TNF receptor-associated factor 3 (TRAF3). This results in an attenuation of the type I IFN signaling pathway. We found that the NS1 C-terminal ED (named NS1/126-225) inhibits the active caspase activation and recruitment domain-containing form of RIG-I [RIG-I(N)]-induced IFN-β reporter activity, the phosphorylation of IRF3, and the induction of IFN-β. Further analysis showed that NS1/126-225 binds to TRAF3 through the TRAF domain, subsequently decreasing TRAF3 K63-linked ubiquitination. NS1/126-225 binding also disrupted the formation of the mitochondrial antiviral signaling (MAVS)–TRAF3 complex, increasing the recruitment of IKKε to MAVS; ultimately shutting down the RIG-I(N)-mediated signal transduction and cellular antiviral responses. This attenuation of cellular antiviral responses leads to evasion of the innate immune response. Taken together, our findings offer an important insight into the interplay between the influenza virus and host innate immunity. url: https://www.ncbi.nlm.nih.gov/pubmed/28717359/ doi: 10.3389/fimmu.2017.00779 id: cord-262375-1ex2ow07 author: Qun, Sen title: Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19 date: 2020-09-02 words: 5187.0 sentences: 280.0 pages: flesch: 50.0 cache: ./cache/cord-262375-1ex2ow07.txt txt: ./txt/cord-262375-1ex2ow07.txt summary: All confirmed patients were clinically classified according to the "Novel Coronavirus Pneumonia Treatment Scheme of the National Health Commission of the People''s Republic of China (version 7)" at the time of admission (4), as follows: (1) general type: symptoms such as fever and respiratory tract complaints were present, and manifestations of pneumonia could be seen on imaging; (2) serious type: any of the following criteria were met: (1) respiratory distress, respiratory rate (RR) ≥ 30 times/min; (2) resting oxygen saturation ≤ 93%; or (3) arterial partial oxygen pressure (PaO 2 )/oxygen absorption concentration (FiO 2 ) ≤ 300 mmHg (1 mmHg = 0.133 kPa); (3) critical type: any of the following criteria were met: (1) respiratory failure and a need for mechanical ventilation, (2) shock, or (3) a combination of factors with other organ failure requiring ICU care. abstract: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. OBJECTIVE: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. METHODS: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. RESULTS: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3(+) and CD8(+) T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). CONCLUSIONS: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19. url: https://doi.org/10.3389/fimmu.2020.02160 doi: 10.3389/fimmu.2020.02160 id: cord-334564-bqh9jkds author: Raony, Ícaro title: Psycho-Neuroendocrine-Immune Interactions in COVID-19: Potential Impacts on Mental Health date: 2020-05-27 words: 9893.0 sentences: 464.0 pages: flesch: 41.0 cache: ./cache/cord-334564-bqh9jkds.txt txt: ./txt/cord-334564-bqh9jkds.txt summary: Since COVID-19 is associated with increased levels of pro-inflammatory cytokines (8) , an immune signature shared with several psychiatric disorders, we propose how the relationship between SARS-CoV-2/host can possibly impair interactions between the immune, nervous and endocrine systems, leading to psychiatric symptoms. Several studies have demonstrated psychiatric manifestations in patients with MERS or SARS during the acute phase, such as increased stress levels, impaired memory, symptoms of depression, anxiety, PTSD, psychoses, and suicidal behavior (28) (29) (30) (31) (32) (33) . If the increase in cytokine levels and the manifestation of psychiatric symptoms are related to the severity of the symptoms of SARS-CoV infection, the "cytokine storm" might also be related to the "mental health thunderstorms" seen in patients with COVID-19? Similar to possible mechanisms involved in the impacts of SARS-CoV-2 infection on mental health, social isolation may also be associated with dysfunctional psycho-neuroendocrine-immune interactions, which in turn can contribute to the development or the worsening of psychiatric disturbances (Figure 2) . abstract: Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The impacts of the disease may be beyond the respiratory system, also affecting mental health. Several factors may be involved in the association between COVID-19 and psychiatric outcomes, such as fear inherent in the pandemic, adverse effects of treatments, as well as financial stress, and social isolation. Herein we discuss the growing evidence suggesting that the relationship between SARS-CoV-2 and host may also trigger changes in brain and behavior. Based on the similarity of SARS-CoV-2 with other coronaviruses, it is conceivable that changes in endocrine and immune response in the periphery or in the central nervous system may be involved in the association between SARS-CoV-2 infection and impaired mental health. This is likely to be further enhanced, since millions of people worldwide are isolated in quarantine to minimize the transmission of SARS-CoV-2 and social isolation can also lead to neuroendocrine-immune changes. Accordingly, we highlight here the hypothesis that neuroendocrine-immune interactions may be involved in negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues. url: https://doi.org/10.3389/fimmu.2020.01170 doi: 10.3389/fimmu.2020.01170 id: cord-325353-tx6s4ggu author: Restori, Katherine H. title: Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma date: 2018-06-04 words: 13653.0 sentences: 618.0 pages: flesch: 42.0 cache: ./cache/cord-325353-tx6s4ggu.txt txt: ./txt/cord-325353-tx6s4ggu.txt summary: The goals of this review are (1) to outline the differences between the neonatal and adult immune systems and (2) to present murine and human data that support the hypothesis that early-life interactions between the immune system and respiratory viruses can create a lung environment conducive to the development of asthma. Because RSV, influenza, and RVs cause a large proportion of respiratorytract infections in neonates, we will focus primarily on these three pathogens as models to better understand how early-life infection and antiviral immune responses might contribute to the subsequent development of asthma. The addition of RSV infection of airway epithelial cells with production of the type-2 innate cytokines, IL-33 (138) , TSLP (123) , and IL-25 (128) , would, therefore, be predicted to create an even more exaggerated type-2-biased microenvironment in the lung with activation of other immune cells (e.g., M2 macrophages, DCs, and/or ILC2 cells) and the development of AHR. abstract: Infants are exposed to a wide range of potential pathogens in the first months of life. Although maternal antibodies acquired transplacentally protect full-term neonates from many systemic pathogens, infections at mucosal surfaces still occur with great frequency, causing significant morbidity and mortality. At least part of this elevated risk is attributable to the neonatal immune system that tends to favor T regulatory and Th2 type responses when microbes are first encountered. Early-life infection with respiratory viruses is of particular interest because such exposures can disrupt normal lung development and increase the risk of chronic respiratory conditions, such as asthma. The immunologic mechanisms that underlie neonatal host–virus interactions that contribute to the subsequent development of asthma have not yet been fully defined. The goals of this review are (1) to outline the differences between the neonatal and adult immune systems and (2) to present murine and human data that support the hypothesis that early-life interactions between the immune system and respiratory viruses can create a lung environment conducive to the development of asthma. url: https://doi.org/10.3389/fimmu.2018.01249 doi: 10.3389/fimmu.2018.01249 id: cord-308433-vrkdtrfz author: Roberts, Ceri A. title: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells date: 2017-02-15 words: 7283.0 sentences: 409.0 pages: flesch: 56.0 cache: ./cache/cord-308433-vrkdtrfz.txt txt: ./txt/cord-308433-vrkdtrfz.txt summary: Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4 + T cell/monocyte cocultures led to increased percentages of IL-10 + cells in pro-inflammatory IL-17 + , IFNγ + , TNFα + , GM-CSF + , and IL-4 + CD4 + T cell subpopulations. To investigate whether TNF blockade regulates IL-10 expression in different pro-inflammatory cytokine-producing CD4 + T cells, we isolated CD4 + T cells from PB of healthy donors and cocultured the cells with CD14 + monocytes and anti-CD3 mAb (100 ng/ml) in the absence or presence of the anti-TNF mAb adalimumab (1 µg/ml), as previously described (20) . abstract: CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy. url: https://doi.org/10.3389/fimmu.2017.00157 doi: 10.3389/fimmu.2017.00157 id: cord-273277-4ewvwg4o author: Rudd, Christopher E. title: GSK-3 Inhibition as a Therapeutic Approach Against SARs CoV2: Dual Benefit of Inhibiting Viral Replication While Potentiating the Immune Response date: 2020-06-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The SARS-CoV2 (COVID-19) pandemic and uncertainties in developing a vaccine have created an urgent need for new therapeutic approaches. A key question is whether it is possible to make rational predictions of new therapies based on the presently available scientific and medical information. In this regard, I have noticed an omission in the present analysis in the literature related to the exploitation of glycogen synthase kinase 3 (GSK-3) as a therapeutic approach. This is based on two key observations, that GSK-3 inhibitors can simultaneously block SARs viral replication, while boosting CD8+ adaptive T-cell and innate natural killer (NK) responses. Firstly, it is already clear that GSK-3 phosphorylation of SARs CoV1 N protein on key serine residues is needed for viral replication such that small molecule inhibitors (SMIs) of GSK-3 can inhibit viral replication. In comparing protein sequences, I show here that the key sites in the N protein of SARs CoV1 N for replication are conserved in SARs CoV2. This strongly suggests that GSK-3 SMIs will also inhibit SARs Cov2 replication. Secondly, we and others have previously documented that GSK-3 SMIs markedly enhance CD8+ cytolytic T-cell (CTL) and NK cell anti-viral effector functions leading to a reduction in both acute and chronic viral infections in mice. My hypothesis is that the repurposing of low-cost inhibitors of GSK-3 such as lithium will limit SARS-CoV2 infections by both reducing viral replication and potentiating the immune response against the virus. To date, there has been no mention of this dual connection between GSK-3 and SARs CoV2 in the literature. To my knowledge, no other drugs exist with the potential to simultaneously target both viral replication and immune response against SARs CoV2. url: https://doi.org/10.3389/fimmu.2020.01638 doi: 10.3389/fimmu.2020.01638 id: cord-350492-1s6wtj25 author: Ruscitti, Piero title: Severe COVID-19, Another Piece in the Puzzle of the Hyperferritinemic Syndrome. An Immunomodulatory Perspective to Alleviate the Storm date: 2020-05-28 words: 3728.0 sentences: 154.0 pages: flesch: 29.0 cache: ./cache/cord-350492-1s6wtj25.txt txt: ./txt/cord-350492-1s6wtj25.txt summary: On these bases, we aimed to review the similarities between severe COVID-19 and diseases included in hyperferritinemic syndrome, from a pathogenic, clinical, and therapeutic point of view, thus proposing new insights to improve the management of those patients. In addition, it has been shown that increased amounts of pro-inflammatory cytokines, including IL-1β, IL-6, IL-12, IFN-γ, IP-10, and MCP1, were associated with pulmonary inflammation and extensive lung damage in SARS patients (25) , thus suggesting a further pathogenic loop in inducing the cytokine storm. The final result is the uncontrolled proliferation of activated immune cells, the massive production of pro-inflammatory mediators, and the development of cytokine storm syndrome, either in severe COVID-19 or SJIA. Considering the lack of efficacy of antiviral therapy for severe coronavirus infection, it is reasonable to postulate the clinical usefulness of specific immunomodulatory therapies (Figure 1) , as observed for other diseases included in hyperferritinemic syndrome such as intravenous immunoglobulins (IVIGs) and tocilizumab, the humanized monoclonal antibody against IL-6 receptor (7). abstract: The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been declared as a worldwide public health emergency. Interestingly, severe COVID-19 is characterized by fever, hyperferritinemia, and a hyper-inflammatory process with a massive release of pro-inflammatory cytokines, which may be responsible for the high rate of mortality. These findings may advocate for a similarity between severe COVID-19 and some challenging rheumatic diseases, such as adult onset Still's disease, secondary hemophagocytic lymphohistiocytosis, and catastrophic anti-phospholipid syndrome, which have been included in the “hyperferritinemic syndrome” category. Furthermore, as performed in these hyper-inflammatory states, severe COVID-19 may benefit from immunomodulatory therapies. url: https://www.ncbi.nlm.nih.gov/pubmed/32574264/ doi: 10.3389/fimmu.2020.01130 id: cord-267134-5gz2dotn author: Sallenave, Jean-Michel title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets? date: 2020-05-28 words: 5347.0 sentences: 239.0 pages: flesch: 39.0 cache: ./cache/cord-267134-5gz2dotn.txt txt: ./txt/cord-267134-5gz2dotn.txt summary: The first anatomical/histological reports from the lungs of severely SARS-CoV-2-affected patients experiencing acute respiratory disease syndrome (ARDS) revealed excessive inflammatory activation and destruction of the bronchial and alveolar epithelium, features already observed during the first SARS pandemics in 2003 (3, 4). The following sections will give an overview of the molecular and cellular mechanisms underpinning SARS-CoV virus infections and how lung and systemic host innate immune responses affect survival either positively, through downregulating the initial viral load, or negatively, by triggering uncontrolled inflammation. Regarding the lung, the differentiated Calu-3 cell line [when cultured at the air-liquid interface (ALI)] is the model of choice: in that set-up, SARS-CoV infection triggered an inflammatory response characterized by increased production of interleukin (IL)-6, IL-8, gamma interferon (IFN-γ), inducible protein 10 (IP-10), and activation of the transcription factor NF-κB (56) . Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus abstract: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described “cytokine storm” and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically. url: https://www.ncbi.nlm.nih.gov/pubmed/32574272/ doi: 10.3389/fimmu.2020.01229 id: cord-267166-ecmayzr6 author: Savarin, Carine title: Distinct Gene Profiles of Bone Marrow-Derived Macrophages and Microglia During Neurotropic Coronavirus-Induced Demyelination date: 2018-06-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination and axonal loss. Demyelinating lesions are associated with infiltrating T lymphocytes, bone marrow-derived macrophages (BMDM), and activated resident microglia. Tissue damage is thought to be mediated by T cell produced cytokines and chemokines, which activate microglia and/or BMDM to both strip myelin and produce toxic factors, ultimately damaging axons and promoting disability. However, the relative contributions of BMDM and microglia to demyelinating pathology are unclear, as their identification in MS tissue is difficult due to similar morphology and indistinguishable surface markers when activated. The CD4 T cell-induced autoimmune murine model of MS, experimental autoimmune encephalitis (EAE), in which BMDM are essential for demyelination, has revealed pathogenic and repair-promoting phenotypes associated with BMDM and microglia, respectively. Using a murine model of demyelination induced by a gliatropic coronavirus, in which BMDM are redundant for demyelination, we herein characterize gene expression profiles of BMDM versus microglia associated with demyelination. While gene expression in CNS infiltrating BMDM was upregulated early following infection and subsequently sustained, microglia expressed a more dynamic gene profile with extensive mRNA upregulation coinciding with peak demyelination after viral control. This delayed microglia response comprised a highly pro-inflammatory and phagocytic profile. Furthermore, while BMDM exhibited a mixed phenotype of M1 and M2 markers, microglia repressed the vast majority of M2-markers. Overall, these data support a pro-inflammatory and pathogenic role of microglia temporally remote from viral control, whereas BMDM retained their gene expression profile independent of the changing environment. As demyelination is caused by multifactorial insults, our results highlight the plasticity of microglia in responding to distinct inflammatory settings, which may be relevant for MS pathogenesis. url: https://www.ncbi.nlm.nih.gov/pubmed/29942315/ doi: 10.3389/fimmu.2018.01325 id: cord-302295-nblmshni author: Savva, Athina title: Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases date: 2013-11-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis. url: https://www.ncbi.nlm.nih.gov/pubmed/24302927/ doi: 10.3389/fimmu.2013.00387 id: cord-313227-6zwkfzab author: Scala, Stefania title: Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs date: 2020-05-27 words: 3872.0 sentences: 202.0 pages: flesch: 36.0 cache: ./cache/cord-313227-6zwkfzab.txt txt: ./txt/cord-313227-6zwkfzab.txt summary: Interestingly, in patients infected by SARS-COv-2, there is an increase in IL1β, IFNγ, IP10, and MCP1, probably leading to activated T-helper-1 (TH1) cell responses, and increased production of T-helper-2 (TH2) immunosuppressive cytokines, such as IL4 and IL10 (18) . Peripheral blood examinations on admission in the majority of patients with COVID-19 displayed lymphopenia, elevated infection-related biomarkers (i.e., procalcitonin, erythrocyte sedimentation rate, serum ferritin, and C-reactive protein) (20) and several elevated inflammatory cytokines (i.e., tumor necrosis factor (TNF)-α, interleukin (IL)-2R and IL-6). Despite markedly reducing virus titers, anti-S-IgG caused lung injury during the early stages of infection, impairing the wound-healing macrophage response and TGF-β production, while promoting pro inflammatory cytokine IL-8, MCP1 production, and inflammatory macrophage accumulation (22) . Another proteasome inhibitor, VR23, possess powerful antiinflammatory activity reducing IL-6 in synovial cells from RA patients, and improving LPS-induced acute lung injury by decreasing neutrophil migration, TNF-α secretion, and tissue inflammation in a mice model (52) . abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15–20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the “pattern recognition receptors” (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the “cytokine storm syndrome,” a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered. url: https://www.ncbi.nlm.nih.gov/pubmed/32574268/ doi: 10.3389/fimmu.2020.01201 id: cord-298458-p7rvupjo author: Schmidt, Megan E. title: The CD8 T Cell Response to Respiratory Virus Infections date: 2018-04-09 words: 8953.0 sentences: 402.0 pages: flesch: 37.0 cache: ./cache/cord-298458-p7rvupjo.txt txt: ./txt/cord-298458-p7rvupjo.txt summary: CD8 T cells play a critical role in mediating viral clearance following many respiratory virus infections including RSV, IAV, and HMPV (25) (26) (27) . In addition, recent murine studies utilizing CD8 T cell epitope-specific immunization strategies observed significantly reduced lung viral titers following IAV, RSV, or SARS challenges (28) (29) (30) . Prime-boosted mice exhibited significantly reduced lung viral titers following RSV, IAV, or SARS infections compared to controls lacking virus-specific memory CD8 T cells. In addition to causing disease in acute respiratory infections, IFN-γ produced by memory CD8 T cells mediated the severe and fatal immunopathology following RSV infection of DC-LM prime-boosted mice (30) . Additionally, robust memory CD8 T cell responses efficiently reduced lung viral titers in the absence of neutralizing antibodies following RSV, IAV, or SARS secondary infections. Despite their benefits in mediating viral clearance and providing protection against secondary infections, memory CD8 T cell responses have been associated with the induction of immunopathology following respiratory virus infections. abstract: Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination. url: https://doi.org/10.3389/fimmu.2018.00678 doi: 10.3389/fimmu.2018.00678 id: cord-351305-6vtv2xuh author: Schramm, Markus A. title: COVID-19 in a Severely Immunosuppressed Patient With Life-Threatening Eosinophilic Granulomatosis With Polyangiitis date: 2020-08-28 words: 1260.0 sentences: 64.0 pages: flesch: 38.0 cache: ./cache/cord-351305-6vtv2xuh.txt txt: ./txt/cord-351305-6vtv2xuh.txt summary: The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA). Thus, due to severity and refractory disease the previously healthy patient was continuously hospitalized from January to March 2020, receiving intravenous cyclophosphamide (CYCLOPS-protocol, cumulative dose 4.76 g), rituximab (4 × 375 mg/m 2 ), and a long-term, slowly tapered high-dose prednisolone treatment (up to 1 g/day). Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients abstract: Immunosuppressive therapies increase the susceptibility of patients to infections. The current pandemic with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compels clinicians to develop recommendations for successful clinical management and surveillance of immunocompromised patients at high risk for severe disease progression. With only few case studies published on SARS-CoV-2 infection in patients with rheumatic diseases, we report a 25-year-old male who developed moderate coronavirus disease 2019 (COVID-19) with fever, mild dyspnea, and no major complications despite having received high-dose prednisolone, cyclophosphamide, and rituximab for the treatment of highly active, life-threatening eosinophilic granulomatosis with polyangiitis (EGPA). url: https://www.ncbi.nlm.nih.gov/pubmed/32983161/ doi: 10.3389/fimmu.2020.02086 id: cord-312955-gs65c3fy author: Schreiber, Gideon title: The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19 date: 2020-09-30 words: 8418.0 sentences: 467.0 pages: flesch: 48.0 cache: ./cache/cord-312955-gs65c3fy.txt txt: ./txt/cord-312955-gs65c3fy.txt summary: Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Thereby, it inhibits the nuclear transport of phosphorylated STAT1, rendering cells refractory to IFN-Is. Another example of viral mechanisms that evolved to eliminate IFN-I functions in inducing innate immunity is given by the SARS corona virus, where both the production of IFNb and the IFN-I induced signaling are attenuated. This gene was found to preferentially cleave the ubiquitin-like modifier interferon-stimulated gene 15 (ISG15), FIGURE 4 | SARS-CoV-2 has multiple effects on the immune system, including inhibition of IFNb production, which results in ISGs not to be produced, CD4+ and CD8+ exhaustion and increased levels of pro-inflammatory proteins (TNFa, IL6, NF-kB). abstract: Type I interferons (IFN-I) were first discovered over 60 years ago in a classical experiment by Isaacs and Lindenman, who showed that IFN-Is possess antiviral activity. Later, it became one of the first approved protein drugs using heterologous protein expression systems, which allowed its large-scale production. It has been approved, and widely used in a pleiotropy of diseases, including multiple-sclerosis, hepatitis B and C, and some forms of cancer. Preliminary clinical data has supported its effectiveness against potential pandemic pathogens such as Ebola and SARS. Still, more efficient and specific drugs have taken its place in treating such diseases. The COVID-19 global pandemic has again lifted the status of IFN-Is to become one of the more promising drug candidates, with initial clinical trials showing promising results in reducing the severity and duration of the disease. Although SARS-CoV-2 inhibits the production of IFNβ and thus obstructs the innate immune response to this virus, it is sensitive to the antiviral activity of externally administrated IFN-Is. In this review I discuss the diverse modes of biological actions of IFN-Is and how these are related to biophysical parameters of IFN-I–receptor interaction and cell-type specificity in light of the large variety of binding affinities of the different IFN-I subtypes towards the common interferon receptor. Furthermore, I discuss how these may guide the optimized use IFN-Is in combatting COVID-19. url: https://doi.org/10.3389/fimmu.2020.595739 doi: 10.3389/fimmu.2020.595739 id: cord-321401-w4ne60fn author: Schrumpf, Jasmijn A. title: Impact of the Local Inflammatory Environment on Mucosal Vitamin D Metabolism and Signaling in Chronic Inflammatory Lung Diseases date: 2020-07-10 words: 10338.0 sentences: 522.0 pages: flesch: 39.0 cache: ./cache/cord-321401-w4ne60fn.txt txt: ./txt/cord-321401-w4ne60fn.txt summary: Evidence for this immunomodulatory and protective role is derived from observational studies showing an association between vitamin D deficiency, chronic airway diseases and respiratory infections, and is supported by a range of experimental studies using cell culture and animal models. Furthermore, recent intervention studies have now shown that vitamin D supplementation reduces exacerbation rates in vitamin D-deficient patients with chronic obstructive pulmonary disease (COPD) or asthma and decreases the incidence of acute respiratory tract infections. Increasing evidence has indicated that vitamin D deficiency is also associated with various other diseases such as cancer, cardiovascular disease, Alzheimer''s disease and muscle myopathy, as well as several immune-related diseases such as type 1 diabetes, multiple sclerosis, inflammatory bowel disease (IBD), psoriasis and chronic inflammatory lung diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD) (6) (7) (8) (9) . abstract: Vitamin D plays an active role in the modulation of innate and adaptive immune responses as well as in the protection against respiratory pathogens. Evidence for this immunomodulatory and protective role is derived from observational studies showing an association between vitamin D deficiency, chronic airway diseases and respiratory infections, and is supported by a range of experimental studies using cell culture and animal models. Furthermore, recent intervention studies have now shown that vitamin D supplementation reduces exacerbation rates in vitamin D-deficient patients with chronic obstructive pulmonary disease (COPD) or asthma and decreases the incidence of acute respiratory tract infections. The active vitamin D metabolite, 1,25-dihydroxy-vitamin D (1,25(OH)(2)D), is known to contribute to the integrity of the mucosal barrier, promote killing of pathogens (via the induction of antimicrobial peptides), and to modulate inflammation and immune responses. These mechanisms may partly explain its protective role against infections and exacerbations in COPD and asthma patients. The respiratory mucosa is an important site of local 1,25(OH)(2)D synthesis, degradation and signaling, a process that can be affected by exposure to inflammatory mediators. As a consequence, mucosal inflammation and other disease-associated factors, as observed in e.g., COPD and asthma, may modulate the protective actions of 1,25(OH)(2)D. Here, we discuss the potential consequences of various disease-associated processes such as inflammation and exposure to pathogens and inhaled toxicants on vitamin D metabolism and local responses to 1,25(OH)(2)D in both immune- and epithelial cells. We furthermore discuss potential consequences of disturbed local levels of 25(OH)D and 1,25(OH)(2)D for chronic lung diseases. Additional insight into the relationship between disease-associated mechanisms and local effects of 1,25(OH)(2)D is expected to contribute to the design of future strategies aimed at improving local levels of 1,25(OH)(2)D and signaling in chronic inflammatory lung diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/32754156/ doi: 10.3389/fimmu.2020.01433 id: cord-312075-asbt0mcj author: Schulz, Katharina S. title: Viral Evasion Strategies in Type I IFN Signaling – A Summary of Recent Developments date: 2016-11-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The immune system protects the organism against infections and the damage associated with them. The first line of defense against pathogens is the innate immune response. In the case of a viral infection, it induces the interferon (IFN) signaling cascade and eventually the expression of type I IFN, which then causes an antiviral state in the cells. However, many viruses have developed strategies to counteract this mechanism and prevent the production of IFN. In order to modulate or inhibit the IFN signaling cascade in their favor, viruses have found ways to interfere at every single step of the cascade, for example, by inducing protein degradation or cleavage, or by mediate protein polyubiquitination. In this article, we will review examples of viruses that modulate the IFN response and describe the mechanisms they use. url: https://www.ncbi.nlm.nih.gov/pubmed/27891131/ doi: 10.3389/fimmu.2016.00498 id: cord-284867-p4jgyusp author: Schöler, Lara title: A Novel In-Cell ELISA Assay Allows Rapid and Automated Quantification of SARS-CoV-2 to Analyze Neutralizing Antibodies and Antiviral Compounds date: 2020-10-09 words: 4328.0 sentences: 235.0 pages: flesch: 42.0 cache: ./cache/cord-284867-p4jgyusp.txt txt: ./txt/cord-284867-p4jgyusp.txt summary: Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. The fact that the infection and the resulting icELISA signal were neutralized by NAbs present in immune sera indicated that the fast and automated icELISA format is applicable for icNTs. Although most SARS-CoV-2 NTs have not been formally validated and certified, classic plaque reduction neutralization tests (PRNT) are currently considered to represent the gold standard for the detection of SARS-CoV-2-specific NAbs. Various commercially available IgM, IgA, and IgG ELISAs have been compared to PRNTs [e.g., (30) ]. Given the excellent signal-to-noise ratio between infected and uninfected cells, the test was applicable to quantify the efficacy of antiviral compounds, here shown for IFNb, and SARS-CoV-2-specific NAbs present in immune sera. abstract: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most pressing medical and socioeconomic challenge. Constituting important correlates of protection, the determination of virus-neutralizing antibodies (NAbs) is indispensable for convalescent plasma selection, vaccine candidate evaluation, and immunity certificates. In contrast to standard serological ELISAs, plaque reduction neutralization tests (PRNTs) are laborious, time-consuming, expensive, and restricted to specialized laboratories. To replace microscopic counting-based SARS-CoV-2 PRNTs by a novel assay exempt from genetically modified viruses, which are inapplicable in most diagnostics departments, we established a simple, rapid, and automated SARS-CoV-2 neutralization assay employing an in-cell ELISA (icELISA) approach. After optimization of various parameters such as virus-specific antibodies, cell lines, virus doses, and duration of infection, SARS-CoV-2-infected cells became amenable as direct antigen source for quantitative icELISA. Antiviral agents such as human sera containing NAbs or antiviral interferons dose dependently reduced the SARS-CoV-2-specific signal. Applying increased infectious doses, the icELISA-based neutralization test (icNT) was superior to PRNT in discriminating convalescent sera with high from those with intermediate neutralizing capacities. In addition, the icNT was found to be specific, discriminating between SARS-CoV-2-specific NAbs and those raised against other coronaviruses. Altogether, the SARS-CoV-2 icELISA test allows rapid (<48 h in total, read-out in seconds) and automated quantification of virus infection in cell culture to evaluate the efficacy of NAbs and antiviral drugs using reagents and equipment present in most routine diagnostics departments. url: https://doi.org/10.3389/fimmu.2020.573526 doi: 10.3389/fimmu.2020.573526 id: cord-268483-joiajgs4 author: Shah, Vibhuti Kumar title: Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past date: 2020-08-07 words: 10644.0 sentences: 477.0 pages: flesch: 43.0 cache: ./cache/cord-268483-joiajgs4.txt txt: ./txt/cord-268483-joiajgs4.txt summary: As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. An ELISA-based time kinetics study to detect the COVID-19 specific humoral immune response showed that the patients produced IgM and IgG antibodies that did not cross-react with other human coronaviruses except SARS-CoV. A case study on pediatric patients reports that 5 out of 6 children showed a protective humoral response, with neutralizing IgG and IgM antibodies targeting the N and S-RBD proteins of SARS-CoV-2 (65) . T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice abstract: After the 1918 flu pandemic, the world is again facing a similar situation. However, the advancement in medical science has made it possible to identify that the novel infectious agent is from the coronavirus family. Rapid genome sequencing by various groups helped in identifying the structure and function of the virus, its immunogenicity in diverse populations, and potential preventive measures. Coronavirus attacks the respiratory system, causing pneumonia and lymphopenia in infected individuals. Viral components like spike and nucleocapsid proteins trigger an immune response in the host to eliminate the virus. These viral antigens can be either recognized by the B cells or presented by MHC complexes to the T cells, resulting in antibody production, increased cytokine secretion, and cytolytic activity in the acute phase of infection. Genetic polymorphism in MHC enables it to present some of the T cell epitopes very well over the other MHC alleles. The association of MHC alleles and its downregulated expression has been correlated with disease severity against influenza and coronaviruses. Studies have reported that infected individuals can, after recovery, induce strong protective responses by generating a memory T-cell pool against SARS-CoV and MERS-CoV. These memory T cells were not persistent in the long term and, upon reactivation, caused local damage due to cross-reactivity. So far, the reports suggest that SARS-CoV-2, which is highly contagious, shows related symptoms in three different stages and develops an exhaustive T-cell pool at higher loads of viral infection. As there are no specific treatments available for this novel coronavirus, numerous small molecular drugs that are being used for the treatment of diseases like SARS, MERS, HIV, ebola, malaria, and tuberculosis are being given to COVID-19 patients, and clinical trials for many such drugs have already begun. A classical immunotherapy of convalescent plasma transfusion from recovered patients has also been initiated for the neutralization of viremia in terminally ill COVID-19 patients. Due to the limitations of plasma transfusion, researchers are now focusing on developing neutralizing antibodies against virus particles along with immuno-modulation of cytokines like IL-6, Type I interferons (IFNs), and TNF-α that could help in combating the infection. This review highlights the similarities of the coronaviruses that caused SARS and MERS to the novel SARS-CoV-2 in relation to their pathogenicity and immunogenicity and also focuses on various treatment strategies that could be employed for curing COVID-19. url: https://doi.org/10.3389/fimmu.2020.01949 doi: 10.3389/fimmu.2020.01949 id: cord-295302-vwrxentv author: Shivarov, Velizar title: Potential SARS-CoV-2 Preimmune IgM Epitopes date: 2020-04-30 words: 2397.0 sentences: 118.0 pages: flesch: 50.0 cache: ./cache/cord-295302-vwrxentv.txt txt: ./txt/cord-295302-vwrxentv.txt summary: While studying the human public IgM igome as represented by a library of 224,087 linear mimotopes, three exact matches to peptides in the proteins of SARS-CoV-2 were found: two in the open reading frame 1ab and one in the spike protein. For the present study, the degrees of the vertices representing the natural SARS-CoV-2 epitopes, all of which belonged to the giant component, were used as the number of adjacent mimotopes parameter. A simple comparison for exact matches to peptides from the SARS-CoV-2 proteome yielded 3 heptapeptides-two in the open reading frame 1ab ( 3518 AQTGIAV 3524 and 5198 TKGPHEF 5204 ) and one in the spike protein ( 108 TTLDSKT 114 ). This loop is adjacent to the loop representing the epitope of the neutralizing antibody LCA60 on the SARS-CoV spike (8, 9) . Thus, it is quite possible that the SARS-CoV-2 spike epitope TTLDSKT is bound by B cells that will contribute to the induced immune response. abstract: While studying the human public IgM igome as represented by a library of 224,087 linear mimotopes, three exact matches to peptides in the proteins of SARS-CoV-2 were found: two in the open reading frame 1ab and one in the spike protein. Joining the efforts to fast track SARS-CoV-2 vaccine development, here we describe briefly these potential epitopes in comparison to mimotopes representing peptides of SARS-CoV, HCoV 229E and OC43. url: https://www.ncbi.nlm.nih.gov/pubmed/32425955/ doi: 10.3389/fimmu.2020.00932 id: cord-318630-h6j7iqbm author: Sinha, Sushmita title: CD8(+) T-Cells as Immune Regulators of Multiple Sclerosis date: 2015-12-10 words: 9004.0 sentences: 465.0 pages: flesch: 50.0 cache: ./cache/cord-318630-h6j7iqbm.txt txt: ./txt/cord-318630-h6j7iqbm.txt summary: In our studies, we have shown that cytotoxic/suppressor CD8(+) T-cells are CNS antigen-specific, MHC class I-restricted, IFNγand perforin-dependent, and are able to inhibit disease. iNTRODUCTiON Studies addressing the immunobiology of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) have focused on CD4 + T-cells as the main orchestrators of pathogenesis and regulation. Interestingly, immune deviation can be elicited against myelin antigens (61, 62) , pointing to the potential role for Qa-1-restricted CD8 + T-cells in EAE disease. We have also demonstrated that GA treatment induces CD8 + Treg in mice, and that these CD8 + T-cells are required for GA to be therapeutically effective in ameliorating EAE disease (64) . Furthermore, relapses in MS are associated with significantly lower CNS-specific CD8 + T-cell suppressor ability, while this potential in MS patients during quiescence is similar to healthy donors, suggesting a role with disease activity (5) . abstract: The vast majority of studies regarding the immune basis of MS (and its animal model, EAE) have largely focused on CD4(+) T-cells as mediators and regulators of disease. Interestingly, CD8(+) T-cells represent the predominant T-cell population in human MS lesions and are oligoclonally expanded at the site of pathology. However, their role in the autoimmune pathologic process has been both understudied and controversial. Several animal models and MS patient studies support a pathogenic role for CNS-specific CD8(+) T-cells, whereas we and others have demonstrated a regulatory role for these cells in disease. In this review, we describe studies that have investigated the role of CD8(+) T-cells in MS and EAE, presenting evidence for both pathogenic and regulatory functions. In our studies, we have shown that cytotoxic/suppressor CD8(+) T-cells are CNS antigen-specific, MHC class I-restricted, IFNγ- and perforin-dependent, and are able to inhibit disease. The clinical relevance for CD8(+) T-cell suppressive function is best described by a lack of their function during MS relapse, and importantly, restoration of their suppressive function during quiescence. Furthermore, CD8(+) T-cells with immunosuppressive functions can be therapeutically induced in MS patients by glatiramer acetate (GA) treatment. Unlike CNS-specific CD8(+) T-cells, these immunosuppressive GA-induced CD8(+) T-cells appear to be HLA-E restricted. These studies have provided greater fundamental insight into the role of autoreactive as well as therapeutically induced CD8(+) T-cells in disease amelioration. The clinical implications for these findings are immense and we propose that this natural process can be harnessed toward the development of an effective immunotherapeutic strategy. url: https://doi.org/10.3389/fimmu.2015.00619 doi: 10.3389/fimmu.2015.00619 id: cord-300429-b0zev8zb author: Sobocińska, Justyna title: Protein Palmitoylation and Its Role in Bacterial and Viral Infections date: 2018-01-19 words: 13428.0 sentences: 587.0 pages: flesch: 40.0 cache: ./cache/cord-300429-b0zev8zb.txt txt: ./txt/cord-300429-b0zev8zb.txt summary: We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. Given the large variety of chemical reporters preferentially mimicking distinct fatty acids, recent years have witnessed a plethora of chemistry-based proteomic studies not only on palmitoylated but also myristoylated proteins and proteins bearing the GPI anchor, including those of pathogens and immune cells (10, 14, 85, 86, 114) The aBe Method Reveals Protein The envelope is rich in transmembrane, often S-palmitoylated, glycoproteins called spikes, which can bind to cognate receptors on the host cell plasma membrane triggering endocytosis of the virion, mediate subsequent fusion of the viral and cellular membranes allowing entry of the viral genome to the cytoplasm, and are also involved in the budding of newly formed virus particles from the cell. abstract: S-palmitoylation is a reversible, enzymatic posttranslational modification of proteins in which palmitoyl chain is attached to a cysteine residue via a thioester linkage. S-palmitoylation determines the functioning of proteins by affecting their association with membranes, compartmentalization in membrane domains, trafficking, and stability. In this review, we focus on S-palmitoylation of proteins, which are crucial for the interactions of pathogenic bacteria and viruses with the host. We discuss the role of palmitoylated proteins in the invasion of host cells by bacteria and viruses, and those involved in the host responses to the infection. We highlight recent data on protein S-palmitoylation in pathogens and their hosts obtained owing to the development of methods based on click chemistry and acyl-biotin exchange allowing proteomic analysis of protein lipidation. The role of the palmitoyl moiety present in bacterial lipopolysaccharide and lipoproteins, contributing to infectivity and affecting recognition of bacteria by innate immune receptors, is also discussed. url: https://www.ncbi.nlm.nih.gov/pubmed/29403483/ doi: 10.3389/fimmu.2017.02003 id: cord-274557-2071770h author: Späth, Peter J. title: On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events date: 2015-02-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates. url: https://www.ncbi.nlm.nih.gov/pubmed/25699039/ doi: 10.3389/fimmu.2015.00011 id: cord-277529-z2r14w2k author: Stella, Alessandro title: Familial Mediterranean Fever and COVID-19: Friends or Foes? date: 2020-09-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Familial Mediterranean Fever (FMF) and COVID-19 show a remarkable overlap of clinical symptoms and similar laboratory findings. Both are characterized by fever, abdominal/chest pain, elevation of C-reactive protein, and leukocytosis. In addition, colchicine and IL-1 inhibitors treatments that are effective in controlling inflammation in FMF patients have recently been proposed for off-label use in COVID-19 patients. Thus, FMF may resemble a milder recapitulation of the cytokine storm that is a hallmark of COVID-19 patients progressing to severe disease. We analyzed the sequence of the MEFV-encoded Pyrin protein – whose mutations cause FMF- in mammals, bats and pangolin. Intriguingly, although Pyrin is extremely conserved in species that are considered either a reservoir or intermediate hosts for SARS-CoV-2, some of the most common FMF-causing variants in humans are present as wildtype residues in these species. We propose that in humans, Pyrin may have evolved to fight highly pathogenic infections. url: https://doi.org/10.3389/fimmu.2020.574593 doi: 10.3389/fimmu.2020.574593 id: cord-288496-7rrh2gg6 author: Stryhn, Anette title: A Systematic, Unbiased Mapping of CD8(+) and CD4(+) T Cell Epitopes in Yellow Fever Vaccinees date: 2020-08-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Examining CD8(+) and CD4(+) T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8(+) and 50 CD4(+) T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4(+) T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4(+) T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4(+) T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4(+) and/or CD8(+) T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4(+) and CD8(+) T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses. url: https://www.ncbi.nlm.nih.gov/pubmed/32983097/ doi: 10.3389/fimmu.2020.01836 id: cord-000647-uofygmeu author: Stäger, Simona title: CD8(+) T Cells in Leishmania Infections: Friends or Foes? date: 2012-01-24 words: 6676.0 sentences: 307.0 pages: flesch: 46.0 cache: ./cache/cord-000647-uofygmeu.txt txt: ./txt/cord-000647-uofygmeu.txt summary: However, since CTLs have been www.frontiersin.org observed in various mouse models and also in human patients, a possible protective role for Leishmania-specific cytotoxic T cells should not be excluded. major infection became less important also because of the strong evidence that Th1 cells were the primary cells involved in mediating protection against cutaneous leishmaniasis (Reiner and Locksley, 1995; Louis et al., 1998; Sacks and Noben-Trauth, 2002) . Vaccination of humans with heat-killed Leishmania or recombinant parasite proteins has so far failed to induce long-term immunity and only recovery from natural or experimental infection has provided proper protection. Pilot studies in the murine model of VL have also demonstrated that adoptive transfer of antigen-specific CD8 + T cells (Polley et al., 2006) or reactivation of CD8 + T cell responses through a therapeutic vaccine (Joshi et al., 2009) results in the control of parasite growth. abstract: Host protection against several intracellular pathogens requires the induction of CD8(+) T cell responses. CD8(+) T cells are potent effector cells that can produce high amounts of pro-inflammatory cytokines and kill infected target cells efficiently. However, a protective role for CD8(+) T cells during Leishmania infections is still controversial and largely depends on the infection model. In this review, we discuss the role of CD8(+) T cells during various types of Leishmania infections, following vaccination, and as potential immunotherapeutic targets. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342007/ doi: 10.3389/fimmu.2012.00005 id: cord-296585-yfh5d4io author: Su, Yu-Ching title: The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeable Haemophilus influenzae date: 2018-11-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Chronic obstructive pulmonary disease (COPD) is a debilitating respiratory disease and one of the leading causes of morbidity and mortality worldwide. It is characterized by persistent respiratory symptoms and airflow limitation due to abnormalities in the lower airway following consistent exposure to noxious particles or gases. Acute exacerbations of COPD (AECOPD) are characterized by increased cough, purulent sputum production, and dyspnea. The AECOPD is mostly associated with infection caused by common cold viruses or bacteria, or co-infections. Chronic and persistent infection by non-typeable Haemophilus influenzae (NTHi), a Gram-negative coccobacillus, contributes to almost half of the infective exacerbations caused by bacteria. This is supported by reports that NTHi is commonly isolated in the sputum from COPD patients during exacerbations. Persistent colonization of NTHi in the lower airway requires a plethora of phenotypic adaptation and virulent mechanisms that are developed over time to cope with changing environmental pressures in the airway such as host immuno-inflammatory response. Chronic inhalation of noxious irritants in COPD causes a changed balance in the lung microbiome, abnormal inflammatory response, and an impaired airway immune system. These conditions significantly provide an opportunistic platform for NTHi colonization and infection resulting in a “vicious circle.” Episodes of large inflammation as the consequences of multiple interactions between airway immune cells and NTHi, accumulatively contribute to COPD exacerbations and may result in worsening of the clinical status. In this review, we discuss in detail the interplay and crosstalk between airway immune residents and NTHi, and their effect in AECOPD for better understanding of NTHi pathogenesis in COPD patients. url: https://doi.org/10.3389/fimmu.2018.02530 doi: 10.3389/fimmu.2018.02530 id: cord-030385-btf502ju author: Sun, Zhiheng title: 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date: 2020-07-22 words: 5855.0 sentences: 328.0 pages: flesch: 55.0 cache: ./cache/cord-030385-btf502ju.txt txt: ./txt/cord-030385-btf502ju.txt summary: However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively. abstract: Sepsis is more common among males than females, and the unequal estrogen levels have been suspected to play a vital role in gender differences. Recently, trained immunity is reported to be a novel strategy for the innate immune system to fight infection. However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. In this study, sepsis was induced in mice by intraperitoneal injection of Escherichia coli (E. coli). The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. For in vitro studies, different macrophages were treated with LPS. The function of estradiol (E2) on macrophage cell lines was verified and the mechanism of E2 affecting trained immunity was explored. We demonstrated that β-glucan-induced trained immunity was more resistant to sepsis in female than male mice. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Moreover, ovariectomized (OVX) mice manifested serious sepsis consequences with a weaker trained immunity effect than female mice. Female bone marrow-derived macrophages (BMDMs) were also apt to be polarized to the M1 phenotype in response to trained immunity in vitro. Furthermore, E2 promoted trained immunity in macrophage cell lines J774 and RAW264.7. E2 was also verified to facilitate trained immunity in primary BMDMs from female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. This study is the first to indicate the role of E2 in the trained immunity induced by β-glucan to protect against E. coli-induced sepsis via the non-canonical NFκB pathway. These results improve our understanding of the molecular mechanisms governing trained immunity in gender differences. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387432/ doi: 10.3389/fimmu.2020.01591 id: cord-256582-x2grfhov author: Sung, Pei-Shan title: CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections date: 2019-12-06 words: 5211.0 sentences: 237.0 pages: flesch: 35.0 cache: ./cache/cord-256582-x2grfhov.txt txt: ./txt/cord-256582-x2grfhov.txt summary: Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). Among these Sykcoupled C-type lectins, activation of CLEC5A by flaviviruses and influenza virus induces the production of inflammatory cytokines and NETosis, while these viruses also activate CLEC2 in platelets to elease extracellular vesicles (EVs), which further enhance inflammatory cytokine release and NETosis via CLEC5A and TLR2 in macrophages and neutrophils. Thus, blockade of CLEC5A-mediated signaling in DV infected cells provides a promising strategy for attenuating systemic vascular leakage and increasing the survival rate of patients suffering from DHF/DSS; this approach might also be applicable to other virus-induced inflammatory diseases (1). These viruses are captured by high affinity receptors (DC-SIGN and MR) to induce inflammatory cytokine release via activation of CLEC5A and CLEC2. Extracellular vesicles from CLEC2-activated platelets enhance dengue virus-induced lethality via CLEC5A/TLR2 abstract: The protective roles of endosomal toll-like receptors (TLRs) and cytosolic nucleic acid sensors are well elucidated, but the pathogenic host factors during viral infections remain unclear. Spleen tyrosine kinase (Syk)-coupled C-type lectins (CLECs) CLEC2 and CLEC5A are highly expressed on platelets and myeloid cells, respectively. CLEC2 has been shown to recognize snake venom aggretin and the endogenous ligand podoplanin and acts as a critical regulator in the development and immunothrombosis. Although CLEC2 has been reported to interact with type I immunodeficiency virus (HIV-1), its role in viral infections is still unclear. CLEC5A binds to fucose and mannose moieties of dengue virus membrane glycans, as well as to N-acetylglucosamine (GlcNAc)/N-acetylmuramic acid (MurNAc) disaccharides that form the backbone of L. monocytogenes peptidoglycans. Recently, we demonstrated that both CLEC2 and CLEC5A are critical in microbe-induced “neutrophil extracellular trap” (NET) formation and proinflammatory cytokine production. Moreover, activation of CLEC2 by dengue virus (DV) and H5N1 influenza virus (IAV) induces the release of extracellular vesicles (EVs), which further enhance NETosis and proinflammatory cytokine production via CLEC5A and Toll-like receptor 2 (TLR2). These findings not only illustrate the immunomodulatory effects of EVs during platelet-leukocyte interactions, but also demonstrate the critical roles of CLEC2 and CLEC5A in acute viral infections. url: https://www.ncbi.nlm.nih.gov/pubmed/31867016/ doi: 10.3389/fimmu.2019.02867 id: cord-353887-f4yd7guj author: Tang, Yujun title: Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies date: 2020-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients. url: https://doi.org/10.3389/fimmu.2020.01708 doi: 10.3389/fimmu.2020.01708 id: cord-255034-x100xo2t author: Theresine, Maud title: Airway Natural Killer Cells and Bacteria in Health and Disease date: 2020-09-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Natural killer (NK) cells are innate lymphoid cells at the interface between innate and adaptive immunity and mostly studied for their important roles in viral infections and malignant tumors. They can kill diseased cells and produce cytokines and chemokines, thereby shaping the adaptive immune response. Nowadays, NK cells are considered as a strong weapon for cancer immunotherapy and can for example be transduced to express tumor-specific chimeric antigen receptors or harnessed with therapeutic antibodies such as the so-called NK engagers. Whereas a large body of literature exists about the antiviral and antitumoral properties of NK cells, their potential role in bacterial infections is not that well delineated. Furthermore, NK cells are much more heterogeneous than previously thought and have tissue-characteristic features and phenotypes. This review gives an overview of airway NK cells and their position within the immunological army dressed against bacterial infections in the upper and predominantly the lower respiratory tracts. Whereas it appears that in several infections, NK cells play a non-redundant and protective role, they can likewise act as rather detrimental. The use of mouse models and the difficulty of access to human airway tissues for ethical reasons might partly explain the divergent results. However, new methods are appearing that are likely to reduce the heterogeneity between studies and to give a more coherent picture in this field. url: https://doi.org/10.3389/fimmu.2020.585048 doi: 10.3389/fimmu.2020.585048 id: cord-319729-6lzjhn8j author: Tian, Bin title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway date: 2018-01-19 words: 7804.0 sentences: 409.0 pages: flesch: 50.0 cache: ./cache/cord-319729-6lzjhn8j.txt txt: ./txt/cord-319729-6lzjhn8j.txt summary: title: Lab-Attenuated Rabies Virus Causes Abortive Infection and Induces Cytokine Expression in Astrocytes by Activating Mitochondrial Antiviral-Signaling Protein Signaling Pathway Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. To assess innate immune responses in astrocytes, cells were infected with DRV or B2c at an MOI of 0.1 and the expression of several proteins involved in the MAVS signaling pathway, namely, RIG-I, p-IRF7, STAT1 and IFIT1 (ISG56), was measured by Western blot. abstract: Rabies is an ancient disease but remains endemic in most parts of the world and causes approximately 59,000 deaths annually. The mechanism through which the causative agent, rabies virus (RABV), evades the host immune response and infects the host central nervous system (CNS) has not been completely elucidated thus far. Our previous studies have shown that lab-attenuated, but not wild-type (wt), RABV activates the innate immune response in the mouse and dog models. In this present study, we demonstrate that lab-attenuated RABV causes abortive infection in astrocytes, the most abundant glial cells in the CNS. Furthermore, we found that lab-attenuated RABV produces more double-stranded RNA (dsRNA) than wt RABV, which is recognized by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5). Activation of mitochondrial antiviral-signaling protein (MAVS), the common adaptor molecule for RIG-I and MDA5, results in the production of type I interferon (IFN) and the expression of hundreds of IFN-stimulated genes, which suppress RABV replication and spread in astrocytes. Notably, lab-attenuated RABV replicates in a manner identical to that of wt RABV in MAVS−/− astrocytes. It was also found that lab-attenuated, but not wt, RABV induces the expression of inflammatory cytokines via the MAVS- p38/NF-κB signaling pathway. These inflammatory cytokines increase the blood–brain barrier permeability and thus enable immune cells and antibodies infiltrate the CNS parenchyma, resulting in RABV control and elimination. In contrast, wt RABV restricts dsRNA production and thus evades innate recognition by RIG-I/MDA5 in astrocytes, which could be one of the mechanisms by which wt RABV evades the host immune response in resident CNS cells. Our findings suggest that astrocytes play a critical role in limiting the replication of lab-attenuated RABV in the CNS. url: https://doi.org/10.3389/fimmu.2017.02011 doi: 10.3389/fimmu.2017.02011 id: cord-354620-xf6glr2h author: Tian, Bin title: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus date: 2020-01-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens. url: https://doi.org/10.3389/fimmu.2019.03131 doi: 10.3389/fimmu.2019.03131 id: cord-003825-tkqxb1ql author: Toman, Miroslav title: Dynamics and Differences in Systemic and Local Immune Responses After Vaccination With Inactivated and Live Commercial Vaccines and Subsequent Subclinical Infection With PRRS Virus date: 2019-08-06 words: 6723.0 sentences: 395.0 pages: flesch: 49.0 cache: ./cache/cord-003825-tkqxb1ql.txt txt: ./txt/cord-003825-tkqxb1ql.txt summary: The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. Comparison of serum and oral fluid antibody responses after vaccination with modified live (MLV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in PRRS endemic farms abstract: The goals of our study were to compare the immune response to different killed and modified live vaccines against PRRS virus and to monitor the antibody production and the cell mediated immunity both at the systemic and local level. In the experiment, we immunized four groups of piglets with two commercial inactivated (A1—Progressis, A2—Suivac) and two modified live vaccines (B3—Amervac, B4—Porcilis). Twenty-one days after the final vaccination, all piglets, including the control non-immunized group (C5), were i.n., infected with the Lelystad strain of PRRS virus. The serum antibody response (IgM and IgG) was the strongest in group A1 followed by two MLV (B3 and B4) groups. Locally, we demonstrated the highest level of IgG antibodies in bronchoalveolar lavages (BALF), and saliva in group A1, whereas low IgA antibody responses in BALF and feces were detected in all groups. We have found virus neutralization antibody at DPV 21 (days post vaccination) and higher levels in all groups including the control at DPI 21 (days post infection). Positive antigen specific cell-mediated response in lymphocyte transformation test (LTT) was observed in groups B3 and B4 at DPV 7 and in group B4 at DPV 21 and in all intervals after infection. The IFN-γ producing lymphocytes after antigen stimulation were found in CD4(−)CD8(+) and CD4(+)CD8(+) subsets of all immunized groups 7 days after infection. After infection, there were obvious differences in virus excretion. The virus was detected in all groups of piglets in serum, saliva, and occasionally in feces at DPI 3. Significantly lower virus load was found in groups A1 and B3 at DPI 21. Negative samples appeared at DPI 21 in B3 group in saliva. It can be concluded that antibodies after immunization and infection, and the virus after infection can be detected in all the compartments monitored. Immunization with inactivated vaccine A1—Progressis induces high levels of antibodies produced both systemically and locally. Immunization with MLV-vaccines (Amervac and Porcilis) produces sufficient antibody levels and also cell-mediated immunity. After infection virus secretion gradually decreases in group B3, indicating tendency to induce sterile immunity. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691355/ doi: 10.3389/fimmu.2019.01689 id: cord-265005-e6rpryrh author: Tomasello, Elena title: Harnessing Mechanistic Knowledge on Beneficial Versus Deleterious IFN-I Effects to Design Innovative Immunotherapies Targeting Cytokine Activity to Specific Cell Types date: 2014-10-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Type I interferons (IFN-I) were identified over 50 years ago as cytokines critical for host defense against viral infections. IFN-I promote anti-viral defense through two main mechanisms. First, IFN-I directly reinforce or induce de novo in potentially all cells the expression of effector molecules of intrinsic anti-viral immunity. Second, IFN-I orchestrate innate and adaptive anti-viral immunity. However, IFN-I responses can be deleterious for the host in a number of circumstances, including secondary bacterial or fungal infections, several autoimmune diseases, and, paradoxically, certain chronic viral infections. We will review the proposed nature of protective versus deleterious IFN-I responses in selected diseases. Emphasis will be put on the potentially deleterious functions of IFN-I in human immunodeficiency virus type 1 (HIV-1) infection, and on the respective roles of IFN-I and IFN-III in promoting resolution of hepatitis C virus (HCV) infection. We will then discuss how the balance between beneficial versus deleterious IFN-I responses is modulated by several key parameters including (i) the subtypes and dose of IFN-I produced, (ii) the cell types affected by IFN-I, and (iii) the source and timing of IFN-I production. Finally, we will speculate how integration of this knowledge combined with advanced biochemical manipulation of the activity of the cytokines should allow designing innovative immunotherapeutic treatments in patients. Specifically, we will discuss how induction or blockade of specific IFN-I responses in targeted cell types could promote the beneficial functions of IFN-I and/or dampen their deleterious effects, in a manner adapted to each disease. url: https://www.ncbi.nlm.nih.gov/pubmed/25400632/ doi: 10.3389/fimmu.2014.00526 id: cord-339152-wfakzb6w author: Trovato, Maria title: Viral Emerging Diseases: Challenges in Developing Vaccination Strategies date: 2020-09-03 words: 12000.0 sentences: 540.0 pages: flesch: 38.0 cache: ./cache/cord-339152-wfakzb6w.txt txt: ./txt/cord-339152-wfakzb6w.txt summary: Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. The occurrence of significant disease outbreaks-such as SARS (severe acute respiratory syndrome) originating in China in 2002 (8) , the 2009 H1N1 swine flu pandemic from Mexico (9) , MERS (Middle East respiratory syndrome) that occurred in Saudi Arabia in 2012 (10) , the West African outbreak of Ebola virus (EBOV) in late 2013 (11) , the Zika virus (ZIKV) outbreak originating in Brazil in 2015 (12) , the 2018 health emergence in Nigeria caused by Lassa virus (13) , and the ongoing Coronavirus disease 2019 (COVID19) pandemic (14) -has renewed interests in developing strategies to faster prevent, treat, and/or control emerging and re-emerging viruses with high epidemic potential. abstract: In the last decades, a number of infectious viruses have emerged from wildlife or re-emerged, generating serious threats to the global health and to the economy worldwide. Ebola and Marburg hemorrhagic fevers, Lassa fever, Dengue fever, Yellow fever, West Nile fever, Zika, and Chikungunya vector-borne diseases, Swine flu, Severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and the recent Coronavirus disease 2019 (COVID-19) are examples of zoonoses that have spread throughout the globe with such a significant impact on public health that the scientific community has been called for a rapid intervention in preventing and treating emerging infections. Vaccination is probably the most effective tool in helping the immune system to activate protective responses against pathogens, reducing morbidity and mortality, as proven by historical records. Under health emergency conditions, new and alternative approaches in vaccine design and development are imperative for a rapid and massive vaccination coverage, to manage a disease outbreak and curtail the epidemic spread. This review gives an update on the current vaccination strategies for some of the emerging/re-emerging viruses, and discusses challenges and hurdles to overcome for developing efficacious vaccines against future pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/33013898/ doi: 10.3389/fimmu.2020.02130 id: cord-323756-atnrw9ew author: Vabret, Nicolas title: Sensing Microbial RNA in the Cytosol date: 2013-12-25 words: 6409.0 sentences: 355.0 pages: flesch: 45.0 cache: ./cache/cord-323756-atnrw9ew.txt txt: ./txt/cord-323756-atnrw9ew.txt summary: When Janeway formulated the theory of pattern recognition in 1989, he proposed that host cells could sense microbial infection owing to receptors able to recognize invariant molecular structures defined as pathogen-associated molecular patterns (PAMPs). They share a similar organization with three distinct domains: (i) a C-terminal repressor domain (RD) embedded within the C-terminal domain (CTD); (ii) a central ATPase containing DExD/H-box helicase domain able to bind RNA; and (iii) a N-terminal tandem CARD domain that mediates downstream signaling, and which is present in RIG-I and MDA5 but absent in LGP2. DDX60 has also been shown to enhance the IFN-I response to RNA and DNA stimulation through formation of complexes with Frontiers in Immunology | Molecular Innate Immunity RIG-I, MDA5, and LGP2 but not with MAVS. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses abstract: The innate immune system faces the difficult task of keeping a fine balance between sensitive detection of microbial presence and avoidance of autoimmunity. To this aim, key mechanisms of innate responses rely on isolation of pathogens in specialized subcellular compartments, or sensing of specific microbial patterns absent from the host. Efficient detection of foreign RNA in the cytosol requires an additional layer of complexity from the immune system. In this particular case, innate sensors should be able to distinguish self and non-self molecules that share several similar properties. In this review, we discuss this interplay between cytosolic pattern recognition receptors and the microbial RNA they detect. We describe how microbial RNAs gain access to the cytosol, which receptors they activate and counter-strategies developed by microorganisms to avoid this response. url: https://www.ncbi.nlm.nih.gov/pubmed/24400006/ doi: 10.3389/fimmu.2013.00468 id: cord-269222-g2ibmo75 author: Valenti, Piera title: Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense date: 2018-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis. url: https://doi.org/10.3389/fimmu.2018.00376 doi: 10.3389/fimmu.2018.00376 id: cord-316702-dj2fo8sn author: Vignesh, Ramachandran title: Is Herd Immunity Against SARS-CoV-2 a Silver Lining? date: 2020-09-30 words: 3250.0 sentences: 169.0 pages: flesch: 45.0 cache: ./cache/cord-316702-dj2fo8sn.txt txt: ./txt/cord-316702-dj2fo8sn.txt summary: Since many studies from different geographical locations are documenting preexisting immunity to SARS-CoV-2, it will be important to define specificities of these T and B cell immune response carefully to assess their association with COVID-19 disease severity. This preexisting cross-reactive T and B cell immunity to SARS-CoV-2 may have wide implications as this could explain differential clinical outcomes in COVID-19 patients, disease severity, vaccine development, and important in accessing herd immunity for SARS-CoV-2 viral infection/COVID-19 disease. Several studies have provided strong evidence for the importance of SARS-CoV-2 specific CTLs, and T helper cells in mild and moderate patients compared to severe COVID-19 disease (27, 28, (31) (32) (33) . Several studies have provided strong evidence for the importance of SARS-CoV-2specific neutralizing antibodies in association with less disease severity in COVID-19 patients (38, 39) . A recent modelling study has estimated that about one in five individuals worldwide would be at increased risk of severe COVID-19, upon infection with SARS-CoV-2, owing to the underlying conditions. abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/33101320/ doi: 10.3389/fimmu.2020.586781 id: cord-004477-qu2o2iu1 author: Vlasova, Anastasia N. title: Editorial: Porcine Anti-Viral Immunity date: 2020-03-06 words: 1583.0 sentences: 88.0 pages: flesch: 45.0 cache: ./cache/cord-004477-qu2o2iu1.txt txt: ./txt/cord-004477-qu2o2iu1.txt summary: Immediately following viral infection, neonatal survival depends on innate immunity and passive protection by lactogenic immune factors such as pathogen-specific antibodies, until an adaptive immune response can develop. Wide-spread porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV) represent major health challenges in the large US swine production systems and possibly worldwide. In introducing the topic of anti-viral immunity, we emphasize the genetic diversity of viruses, the virus life cycle and the pathology that viral infection can cause. A more tedious procedure is to use only parts of the virus as the vaccine (subunit vaccines) that target the immune response to those viral epitopes that elicit VN antibodies. A second approach to vaccine development is use of live attenuated virus that has been genetically modified or cell culture adapted and cannot produce a disease in the host but can still replicate. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067899/ doi: 10.3389/fimmu.2020.00399 id: cord-259748-x7dq1sy4 author: Wan, Dongshan title: Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response date: 2020-04-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Double-stranded DNA (dsDNA) sensor cyclic-GMP-AMP synthase (cGAS) along with the downstream stimulator of interferon genes (STING) acting as essential immune-surveillance mediators have become hot topics of research. The intrinsic function of the cGAS-STING pathway facilitates type-I interferon (IFN) inflammatory signaling responses and other cellular processes such as autophagy, cell survival, senescence. cGAS-STING pathway interplays with other innate immune pathways, by which it participates in regulating infection, inflammatory disease, and cancer. The therapeutic approaches targeting this pathway show promise for future translation into clinical applications. Here, we present a review of the important previous works and recent advances regarding the cGAS-STING pathway, and provide a comprehensive understanding of the modulatory pattern of the cGAS-STING pathway under multifarious pathologic states. url: https://www.ncbi.nlm.nih.gov/pubmed/32411126/ doi: 10.3389/fimmu.2020.00615 id: cord-351431-xcqz9d3t author: Wang, Jun title: Excessive Neutrophils and Neutrophil Extracellular Traps in COVID-19 date: 2020-08-18 words: 4522.0 sentences: 268.0 pages: flesch: 48.0 cache: ./cache/cord-351431-xcqz9d3t.txt txt: ./txt/cord-351431-xcqz9d3t.txt summary: Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Principal component analysis was performed with R package "FactoMineR" to identify those clinical parameters that contribute most to distinguishing severe, moderate, and mild cases of COVID-19 (28) . For BALF, the most upregulated marker genes were similarly enriched in neutrophils, but more up-regulated genes in monocytes and B cells were observed in COVID-19 patients compared to healthy controls, which is different from the lung samples. Transcriptome analysis of lung specimens and BALF from COVID-19 patients also indicated the most up-regulated marker genes were neutrophil related. Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19 abstract: Background: Cases of excessive neutrophil counts in the blood in severe coronavirus disease (COVID-19) patients have drawn significant attention. Neutrophil infiltration was also noted on the pathological findings from autopsies. It is urgent to clarify the pathogenesis of neutrophils leading to severe pneumonia in COVID-19. Methods: A retrospective analysis was performed on 55 COVID-19 patients classified as mild (n = 22), moderate (n = 25), and severe (n = 8) according to the Guidelines released by the National Health Commission of China. Trends relating leukocyte counts and lungs examined by chest CT scan were quantified by Bayesian inference. Transcriptional signatures of host immune cells of four COVID19 patients were analyzed by RNA sequencing of lung specimens and BALF. Results: Neutrophilia occurred in 6 of 8 severe patients at 7–19 days after symptom onset, coinciding with lesion progression. Increasing neutrophil counts paralleled lesion CT values (slope: 0.8 and 0.3–1.2), reflecting neutrophilia-induced lung injury in severe patients. Transcriptome analysis revealed that neutrophil activation was correlated with 17 neutrophil extracellular trap (NET)-associated genes in COVID-19 patients, which was related to innate immunity and interacted with T/NK/B cells, as supported by a protein–protein interaction network analysis. Conclusion: Excessive neutrophils and associated NETs could explain the pathogenesis of lung injury in COVID-19 pneumonia. url: https://doi.org/10.3389/fimmu.2020.02063 doi: 10.3389/fimmu.2020.02063 id: cord-003914-ss8vdpox author: Wang, Shenghua title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection date: 2019-10-02 words: 4829.0 sentences: 229.0 pages: flesch: 48.0 cache: ./cache/cord-003914-ss8vdpox.txt txt: ./txt/cord-003914-ss8vdpox.txt summary: title: Oral Immunization of Chickens With Recombinant Lactobacillus plantarum Vaccine Against Early ALV-J Infection plantarum) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed. plantarum group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection. The ALV-J-NX0101 strain, pMD18T-env recombinant vector (containing the gp85 gene), gp85-specific mouse monoclonal anti-body (MAb JE9), ALV-J antibody test kit, and ALV P27 antigen enzyme-linked immunosorbent assay (ELISA) test kits (IDEXX USA Inc., Beijing, China) were donated by Prof. plantarum significantly triggered specific IgG and IgA antibodies against ALV-J, and enhanced the levels of IgG and sIgA compared to the control group (Figures 4, 5) . This study described the mucosal and systemic immune responses specific to ALV-J induced by an orally administered recombinant L. abstract: In this study, a novel oral vaccine of recombinant Lactobacillus plantarum (L. plantarum) containing the gp85 protein was explored, and the effects of this vaccine on the prevention of subgroup J Avian Leukosis Virus (ALV-J) infection were assessed. In the current study, the gp85 protein of ALV-J was expressed on the surface of L. plantarum with the surface-display motif, pgsA, by constructing a shuttle vector pMG36e:pgsA:gp85. Surface localization of the fusion protein was verified by western blotting and flow cytometry. Subsequently, Specific Pathogen Free Hy-Line Brown layer chickens were orally vaccinated with the recombinant L. plantarum and presented with high levels of serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA) titers in bile and duodenal-mucosal fluid. After challenged with ALV-J of a 3 × 10(3) 50% tissue culture infective dose (TCID50), serum samples of the chickens were collected and viremia was analyzed. Results showed that, compared to the L. plantarum and PBS control group, the recombinant L. plantarum group showed a significant rise in antibody levels after inoculation, and provide improved protection against ALV-J according to viremia detection. These results indicate that oral immunization with the recombinant L. plantarum provided an effective means for eliciting protective immune response against early ALV-J infection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783503/ doi: 10.3389/fimmu.2019.02299 id: cord-344610-mqq6fmsp author: Waumans, Yannick title: The Dipeptidyl Peptidase Family, Prolyl Oligopeptidase, and Prolyl Carboxypeptidase in the Immune System and Inflammatory Disease, Including Atherosclerosis date: 2015-08-07 words: 9097.0 sentences: 481.0 pages: flesch: 42.0 cache: ./cache/cord-344610-mqq6fmsp.txt txt: ./txt/cord-344610-mqq6fmsp.txt summary: Usually only four prolyl-specific peptidases are considered: DPPIV (EC 3.4.14.5), fibroblast activation protein α (FAP; EC 3.4.21.B28), and the more recently discovered DPP8 and DPP9 (EC 3.4.14). However, due to similarities in substrate specificity and structural homology, it is more relevant to consider a broader family that also includes prolyl oligopeptidase (PREP; EC 3.4.21.26), dipeptidyl peptidase II (DPPII) (EC 3.4.14.2), and prolyl carboxypeptidase (PRCP; EC 3.4.16.2). Three other studies also found no to low DPPIV expression or activity associated with human monocytes and/or macrophages (82, [136] [137] [138] . Dipeptidyl peptidase 4 is present in low amounts on freshly isolated human NK cells and its expression is only upregulated in a small subpopulation after IL-2 stimulation (158) . Dipeptidyl peptidase 8 and 9 have been found to be abundantly present in the macrophage-rich regions of human atherosclerotic plaques and considering DPP9''s role in macrophage activation, it might potentially be involved in atherogenesis (82). Expression and functional role of dipeptidyl peptidase IV (CD26) on human natural killer cells abstract: Research from over the past 20 years has implicated dipeptidyl peptidase (DPP) IV and its family members in many processes and different pathologies of the immune system. Most research has been focused on either DPPIV or just a few of its family members. It is, however, essential to consider the entire DPP family when discussing any one of its members. There is a substantial overlap between family members in their substrate specificity, inhibitors, and functions. In this review, we provide a comprehensive discussion on the role of prolyl-specific peptidases DPPIV, FAP, DPP8, DPP9, dipeptidyl peptidase II, prolyl carboxypeptidase, and prolyl oligopeptidase in the immune system and its diseases. We highlight possible therapeutic targets for the prevention and treatment of atherosclerosis, a condition that lies at the frontier between inflammation and cardiovascular disease. url: https://www.ncbi.nlm.nih.gov/pubmed/26300881/ doi: 10.3389/fimmu.2015.00387 id: cord-003656-7mzsaz7a author: Wium, Martha title: DNA Vaccines Against Mycoplasma Elicit Humoral Immune Responses in Ostriches date: 2019-05-14 words: 5575.0 sentences: 308.0 pages: flesch: 53.0 cache: ./cache/cord-003656-7mzsaz7a.txt txt: ./txt/cord-003656-7mzsaz7a.txt summary: Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. In this study we report, for the first time, that a DNA vaccine can elicit a humoral immune response in ostriches using OppA as antigen. The controls were serum samples representing the week 0, 3, 6, and 9 sampling points of a single ostrich, randomly selected from the pCI-neo_oppA 1,200 µg group based on high titers produced after vaccination. In this study, DNA vaccines were developed for ostriches using the oppA gene of an ostrich-infecting mycoplasma (Ms03) as vaccine antigen. abstract: In ostriches, the population densities resulting from intensive rearing increases susceptibility to pathogens such as mycoplasmas. In addition to good management practices, vaccination offers an attractive alternative for controlling mycoplasma infections in food animals, instead of using antibiotics, which often leave unacceptable residues. The use of live attenuated vaccines, however, carry the concern of reversion to virulence or genetic recombination with field strains. Currently there are no commercially available vaccines against ostrich-infecting mycoplasmas and this study therefore set out to develop and evaluate the use of a DNA vaccine against mycoplasma infections in ostriches using an OppA protein as antigen. To this end, the oppA gene of “Mycoplasma nasistruthionis sp. nov.” str. Ms03 was cloned into two DNA vaccine expression vectors after codon correction by site-directed mutagenesis. Three-months-old ostriches were then vaccinated intramuscularly at different doses followed by a booster vaccination after 6 weeks. The ability of the DNA vaccines to elicit an anti-OppA antibody response was evaluated by ELISA using the recombinant OppA protein of Ms03 as coating antigen. A statistically significant anti-OppA antibody response could be detected after administration of a booster vaccination indicating that the OppA protein was successfully immunogenic. The responses were also both dose and vector dependent. In conclusion, the DNA vaccines were able to elicit an immune response in ostriches and can therefore be viewed as an option for the development of vaccines against mycoplasma infections. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527592/ doi: 10.3389/fimmu.2019.01061 id: cord-275779-ocbygkyb author: Ye, Zi-Wei title: Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice date: 2017-03-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P < 0.0001). The phenotype was potentially due to an exaggerated inflammatory cell infiltration triggered by ADCC, as an upregulated release of cytotoxic granules (perforin) was observed in the lung tissue of E1-vaccinated mice after H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC. url: https://doi.org/10.3389/fimmu.2017.00317 doi: 10.3389/fimmu.2017.00317 id: cord-307813-elom30nx author: Yip, Tsz-Fung title: Advancements in Host-Based Interventions for Influenza Treatment date: 2018-07-10 words: 15075.0 sentences: 735.0 pages: flesch: 38.0 cache: ./cache/cord-307813-elom30nx.txt txt: ./txt/cord-307813-elom30nx.txt summary: Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. A recent study using RNAi also demonstrated that cholesterol homeostasis can be regulated via acid phosphatase 2 (ACP2)-mediated Niemann-Pick C2 activity and impaired the membrane fusion of IAV and influenza B virus (IBV) (52) , further suggesting the importance of controlling cholesterol homeostasis in the release of viral genome to cytoplasm. Furthermore, FPR2 antagonists have been described to possess antiviral activity against not only IAV but also IBV infection (111) , promoting the idea that antagonizing FPR2 to suppress Raf/MEK/ERK signaling cascade could potentially be a novel approach for the treatment of a broad spectrum of influenza viruses. abstract: Influenza is a major acute respiratory infection that causes mortality and morbidity worldwide. Two classes of conventional antivirals, M2 ion channel blockers and neuraminidase inhibitors, are mainstays in managing influenza disease to lessen symptoms while minimizing hospitalization and death in patients with severe influenza. However, the development of viral resistance to both drug classes has become a major public health concern. Vaccines are prophylaxis mainstays but are limited in efficacy due to the difficulty in matching predicted dominant viral strains to circulating strains. As such, other potential interventions are being explored. Since viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, potential targets for drug development include controlling virus-induced host immune responses such as the recently suggested involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis and immune cell metabolism. In this review, we will discuss the advancements in novel host-based interventions for treating influenza disease. url: https://doi.org/10.3389/fimmu.2018.01547 doi: 10.3389/fimmu.2018.01547 id: cord-003378-0ozhye9q author: Yu, Haijing title: Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression date: 2018-12-13 words: 5912.0 sentences: 350.0 pages: flesch: 53.0 cache: ./cache/cord-003378-0ozhye9q.txt txt: ./txt/cord-003378-0ozhye9q.txt summary: In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. Our study found that Fgl2 was highly expressed in peripheral blood mononuclear cells (PBMCs) and in liver tissue of humans or mice with severe viral hepatitis, and was positively related to the severity of the disease (13, 14) . Compared to wild-type mice, CC10-knockout mice exhibited excessive airway inflammation Abbreviations: FH, fulminant hepatitis; MHV-3, murine hepatitis virus strain 3; Fgl2, Fibrinogen-like protein 2; CC10, Clara cell 10 KDa protein; ALF, acute liver failure; PFU, plaque-forming units; PBS, phosphate-buffered saline; ALT, alanine aminotransferase; AST, aspartate aminotransferase; PCA, pro-coagulant activity; HRP, horseradish peroxidase; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling. In this study, we investigated the role of CC10 in hepatitis virus strain 3 (MHV-3)-induced FH in mice and explored whether CC10 protein could regulate Fgl2 in the disease process. abstract: Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10. Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro. Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs). Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300492/ doi: 10.3389/fimmu.2018.02935 id: cord-260452-js4nr4d8 author: Yu, Junyang title: Activation and Role of NACHT, LRR, and PYD Domains-Containing Protein 3 Inflammasome in RNA Viral Infection date: 2017-10-31 words: 4082.0 sentences: 222.0 pages: flesch: 34.0 cache: ./cache/cord-260452-js4nr4d8.txt txt: ./txt/cord-260452-js4nr4d8.txt summary: Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. IL-1β and IL-18 serve to activate myriad downstream cell responses, and orchestrate innate and adaptive immunity through MyD88/IRAK4/TRAF6-mediated NF-κB signaling and the JNK/p38 mitogen-activated protein kinase pathways (60-63), which may represent key events for the NLRP3 inflammasome-dependent antiviral defense. In BV-2 mouse microglia cells infected by Japanese encephalitis virus, the NLRP3 inflammasome induces production of IL-1β and IL-18 rapidly (within 3 h of exposure) and of TNF-α, CCL2, and IL-6 later (within 6 h after exposure) (40) ; the findings suggest that the NLRP3dependent protective inflammatory response is a very early phase innate immune response against RNA viral infection. abstract: NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation and effects during ribonucleic acid (RNA) viral infection are the focus of a wide range of research currently. Both the pathogen-associated molecule pattern derived from virions and intracellular stress molecules involved in the process of viral infection lead to activation of the NLRP3 inflammasome, which in turn triggers inflammatory responses for antiviral defense and tissue healing. However, aberrant activation of the NLRP3 inflammasome can instead support viral pathogenesis and promote disease progression. Here, we summarize and expound upon the recent literature describing the molecular mechanisms underlying the activation and effects of the NLRP3 inflammasome in RNA viral infection to highlight how it provides protection against RNA viral infection. url: https://doi.org/10.3389/fimmu.2017.01420 doi: 10.3389/fimmu.2017.01420 id: cord-328011-6lf3no6u author: Zayed, Hatem title: Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics date: 2020-08-14 words: 1449.0 sentences: 84.0 pages: flesch: 49.0 cache: ./cache/cord-328011-6lf3no6u.txt txt: ./txt/cord-328011-6lf3no6u.txt summary: title: Vaccine Development Against COVID-19 Prior to Pandemic Outbreaks, Using in vitro Evolution and Reverse Genetics Since coronaviruses are increasing alarmingly, there is an urgent need for a safe and effective vaccine to prevent the spread of the virus during pandemic outbreaks, and stop deaths associated with the virulent COVID-19. We now know that SARS-CoV-2 shares 88% identity with two SARS-like coronaviruses (bat-SL-CoVZXC21 and bat-SL-CoVZC45) that both originated in China, and use the same human angiotensin-converting enzyme 2 receptor for cell entry during the process of infection (3). In response to such forewarnings from scientists, a predictive vaccine could have been designed and developed for the potential virus pandemic. Thereafter, during the time of pandemic, suitable stored transgenic cell lines could be used, based on the Abbreviations: COVID-19, coronavirus disease 2019; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VLP, virus-like particle; WHO, World Health Organization. abstract: nan url: https://doi.org/10.3389/fimmu.2020.02051 doi: 10.3389/fimmu.2020.02051 id: cord-263141-n200x6z1 author: Zelaya, Hortensia title: Respiratory Antiviral Immunity and Immunobiotics: Beneficial Effects on Inflammation-Coagulation Interaction during Influenza Virus Infection date: 2016-12-23 words: 8198.0 sentences: 372.0 pages: flesch: 30.0 cache: ./cache/cord-263141-n200x6z1.txt txt: ./txt/cord-263141-n200x6z1.txt summary: Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. Then, our studies were the first in demonstrating a beneficial modulation of the immune-coagulative response during respiratory TRL3 activation and IFV infection induced by immunobiotic microorganisms (Figure 3) . abstract: Influenza virus (IFV) is a major respiratory pathogen of global importance, and the cause of a high degree of morbidity and mortality, especially in high-risk populations such as infants, elderly, and immunocompromised hosts. Given its high capacity to change antigenically, acquired immunity is often not effective to limit IFV infection and therefore vaccination must be constantly redesigned to achieve effective protection. Improvement of respiratory and systemic innate immune mechanisms has been proposed to reduce the incidence and severity of IFV disease. In the last decade, several research works have demonstrated that microbes with the capacity to modulate the mucosal immune system (immunobiotics) are a potential alternative to beneficially modulate the outcome of IFV infection. This review provides an update of the current status on the modulation of respiratory immunity by orally and nasally administered immunobiotics, and their beneficial impact on IFV clearance and inflammatory-mediated lung tissue damage. In particular, we describe the research of our group that investigated the influence of immunobiotics on inflammation–coagulation interactions during IFV infection. Studies have clearly demonstrated that hostile inflammation is accompanied by dysfunctional coagulation in respiratory IFV disease, and our investigations have proved that some immunobiotic strains are able to reduce viral disease severity through their capacity to modulate the immune-coagulative responses in the respiratory tract. url: https://www.ncbi.nlm.nih.gov/pubmed/28066442/ doi: 10.3389/fimmu.2016.00633 id: cord-312074-0nqmjdek author: Zhong, Jixin title: Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease date: 2015-09-25 words: 5420.0 sentences: 253.0 pages: flesch: 36.0 cache: ./cache/cord-312074-0nqmjdek.txt txt: ./txt/cord-312074-0nqmjdek.txt summary: Liebler showed that DPP4 inhibition enhances SDF-1/CXCR4 axis and increased the retention of human bone marrow-derived cells in the injured lungs of immune deficient mice by 30% (71) . It has been shown that parathyroid hormone treatment after myocardial infarction improves DPP4 in chemotaxis and cardiovascular disease Frontiers in Immunology | www.frontiersin.org survival and myocardial function with potential involvement of enhanced homing of bone marrow-derived stem cells. demonstrated that parathyroid hormone serves as a DPP4 inhibitor and increases cardiac SDF-1 level, which in turn enhances CXCR4 + bone marrow-derived stem cell homing to ischemic heart and attenuates ischemic cardiomyopathy after infarction (91) . Suppression of DPP4 enzymatic activities by pharmacological inhibitors preserves SDF-1, which results in an enhanced homing of CXCR4 + progenitor cells from bone marrow to infarcted tissues. abstract: Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-derived factor-1 (SDF-1, also known as CXCL12) is perhaps an increasingly recognized target, given its importance in processes, such as hematopoiesis, angiogenesis, and stem cell homing. In the current review, we will summarize the importance of DPP4-mediated enzymatic processing of cytokines/chemokines with an emphasis on SDF-1 and resultant implications for cardiovascular physiology and disease. url: https://doi.org/10.3389/fimmu.2015.00477 doi: 10.3389/fimmu.2015.00477 id: cord-257116-6td3efjw author: Zhou, Yanrong title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production date: 2017-08-09 words: 5514.0 sentences: 323.0 pages: flesch: 50.0 cache: ./cache/cord-257116-6td3efjw.txt txt: ./txt/cord-257116-6td3efjw.txt summary: title: Cellular RNA Helicase DDX1 Is Involved in Transmissible Gastroenteritis Virus nsp14-Induced Interferon-Beta Production In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEVencoded proteins. Nsp14 interacts with cellular DExD/H helicase DDX1 to activate IFN-β in a NF-κB dependent manner, and DDX1 is associated with TGEV-induced IFN-β production, revealing a potential coactivator role of host RNA helicase DDX1 on virus and viral protein induced innate immune responses. abstract: Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus (CoV) of porcine, causes lethal watery diarrhea and severe dehydration in piglets and leads to severe economic losses in the swine industry. Unlike most CoVs that antagonize type I interferon (IFN) production, previous studies showed that TGEV infection induces IFN-I production both in vivo and in vitro. However, the underlying mechanism(s) remain largely unknown. In this study, we found that TGEV infection significantly facilitated IFN-β production as well as activation of the transcription factors IFN regulatory factor 3 (IRF3) and nuclear factor-kappaB (NF-κB) in porcine kidney (PK-15) cells. Screening of TGEV-encoded proteins demonstrated that non-structural protein 14 (nsp14) was the most potent IFN-β inducer and induced IFN-β production mainly by activating NF-κB but not IRF3. Further analysis showed that nsp14 interacted with DDX1, a member of the DExD/H helicase family. Knockdown of DDX1 by specific small interfering RNA (siRNA) significantly decreased nsp14-induced IFN-β production and NF-κB activation. Furthermore, TGEV-induced IFN-β production and IFN-stimulated gene (ISG) expression were decreased in cells transfected with DDX1-specific siRNA, indicating the vital role of DDX1 to TGEV-induced IFN-β responses. In summary, our data revealed a potential coactivator role of host RNA helicase DDX1 to the induction of IFN-β response initiated by TGEV and demonstrated that nsp14 is an important IFN inducer among the TGEV-encoded proteins. url: https://doi.org/10.3389/fimmu.2017.00940 doi: 10.3389/fimmu.2017.00940 id: cord-003828-bhfghcby author: Zrzavy, Tobias title: Vaccination in Multiple Sclerosis: Friend or Foe? date: 2019-08-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Multiple sclerosis (MS) is a debilitating disease of the central nervous systems (CNS). Disease-modifying treatments (including immunosuppressive treatments) have shown positive effects on the disease course, but are associated with systemic consequences on the immune system and may increase the risk of infections and alter vaccine efficiency. Therefore, vaccination of MS patients is of major interest. Over the last years, vaccine hesitancy has steadily grown especially in Western countries, partly due to fear of sequelae arising from vaccination, especially neurological disorders. The interaction of vaccination and MS has been discussed for decades. In this review, we highlight the immunology of vaccination, provide a review of literature and discuss the clinical consideration of MS, vaccination and immunosuppression. In conclusion, there is consensus that MS cannot be caused by vaccines, neither by inactivated nor by live vaccines. However, particular attention should be paid to two aspects: First, in immunocompromised patients, live vaccines may lead to a stronger immune reaction with signs of the disease against which the patients have been vaccinated, albeit in weakened form. Second, protection provided by vaccination should be controlled in patients who have been vaccinated while receiving immunomodulatory or immunosuppressive treatment. In conclusion, there is evidence that systemic infections can worsen MS, thus vaccination will lower the risk of relapses by reducing the risk of infections. Therefore, vaccination should be in general recommended to MS patients. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693409/ doi: 10.3389/fimmu.2019.01883 id: cord-353217-gmc3qrci author: de Miranda Santos, Isabel Kinney Ferreira title: Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus date: 2020-08-04 words: 551.0 sentences: 34.0 pages: flesch: 36.0 cache: ./cache/cord-353217-gmc3qrci.txt txt: ./txt/cord-353217-gmc3qrci.txt summary: Recent large observational studies indicate that hydroxychloroquine (HY) does not affect outcomes of patients hospitalized with COVID-19 (1, 2) and may even be harmful (3) . In view of this situation and of the importance of correct interpretation of antibody profiles for planning preventive measures for COVID-19, we would like to bring the attention of readers to studies that raise concerns about the possible impact of HY upon antibody responses to SARS-CoV-2. To the best of our knowledge, there are no new facts in the scientific and medical literature that indicate that the same mechanism could not operate in HY-treated patients suffering from COVID-19 and negatively impact their SARS-CoV-2-specific antibody responses. As more needs to be learned about the role of antibodies in recovery from and protection against infection with SARS-CoV-2, the impact of HY and other treatment regimens on antibody responses requires systematic evaluation. abstract: nan url: https://doi.org/10.3389/fimmu.2020.01739 doi: 10.3389/fimmu.2020.01739 id: cord-344829-adlp2rjy author: de Rivero Vaccari, Juan Carlos title: The Inflammasome in Times of COVID-19 date: 2020-10-08 words: 8722.0 sentences: 423.0 pages: flesch: 37.0 cache: ./cache/cord-344829-adlp2rjy.txt txt: ./txt/cord-344829-adlp2rjy.txt summary: Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients. Here we review the literature on the role of the inflammasome in CoV infections, which includes how CoVs activate inflammasomes upon infection, the role of the inflammasome in acute respiratory distress syndrome (ARDS), how ventilator-induced lung injury (VILI) activates the inflammasome, how the inflammasome plays a role in the systemic complications associated with COVID-19, and how the inflammasome is involved in the process of Disseminated Intravascular Coagulation (DIC). abstract: Coronaviruses (CoVs) are members of the genus Betacoronavirus and the Coronaviridiae family responsible for infections such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and more recently, coronavirus disease-2019 (COVID-19). CoV infections present mainly as respiratory infections that lead to acute respiratory distress syndrome (ARDS). However, CoVs, such as COVID-19, also present as a hyperactivation of the inflammatory response that results in increased production of inflammatory cytokines such as interleukin (IL)-1β and its downstream molecule IL-6. The inflammasome is a multiprotein complex involved in the activation of caspase-1 that leads to the activation of IL-1β in a variety of diseases and infections such as CoV infection and in different tissues such as lungs, brain, intestines and kidneys, all of which have been shown to be affected in COVID-19 patients. Here we review the literature regarding the mechanism of inflammasome activation by CoV infection, the role of the inflammasome in ARDS, ventilator-induced lung injury (VILI), and Disseminated Intravascular Coagulation (DIC) as well as the potential mechanism by which the inflammasome may contribute to the damaging effects of inflammation in the cardiac, renal, digestive, and nervous systems in COVID-19 patients. url: https://www.ncbi.nlm.nih.gov/pubmed/33149733/ doi: 10.3389/fimmu.2020.583373 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel