{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T02:14:17Z","timestamp":1782267257585,"version":"3.54.5"},"reference-count":131,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Respir Crit Care Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Biomedical research has long strived to improve our understanding of the immune response to respiratory viral infections, an effort that has become all the more important as we live through the consequences of a pandemic. The disease course of these infections is shaped in large part by the actions of various cells of the innate and adaptive immune systems. While these cells are crucial in clearing viral pathogens and establishing long-term immunity, their effector mechanisms may also escalate into excessive, tissue-destructive inflammation detrimental to the host. In this review, we describe the breadth of the immune response to infection with respiratory viruses such as influenza and respiratory syncytial virus. Throughout, we focus on the host rather than the pathogen and try to describe shared patterns in the host response to different viruses. We start with the local cells of the airways, onto the recruitment and activation of innate and adaptive immune cells, followed by the establishment of local and systemic memory cells key in protection against reinfection. We end by exploring how respiratory viral infections can predispose to bacterial superinfection.<\/jats:p>","DOI":"10.1055\/s-0041-1736459","type":"journal-article","created":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T01:09:12Z","timestamp":1639703352000},"page":"759-770","source":"Crossref","is-referenced-by-count":10,"title":["The Immune Response to Respiratory Viruses: From Start to Memory"],"prefix":"10.1055","volume":"42","author":[{"given":"Tom D.Y.","family":"Reijnders","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex R.","family":"Schuurman","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[{"name":"Center for Experimental and Molecular Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands"},{"name":"Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2021,12,16]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s00281-016-0558-0","article-title":"The host immune response in respiratory virus infection: balancing virus clearance and immunopathology","volume":"38","author":"A H Newton","year":"2016","journal-title":"Semin Immunopathol"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S2213-2600(21)00218-6","article-title":"The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity","volume":"9","author":"M F Osuchowski","year":"2021","journal-title":"Lancet Respir Med"},{"issue":"07","key":"ref3","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cell.2021.02.029","article-title":"COVID-19 and the human innate immune system","volume":"184","author":"J L Schultze","year":"2021","journal-title":"Cell"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2021.01.007","article-title":"Adaptive immunity to SARS-CoV-2 and COVID-19","volume":"184","author":"A Sette","year":"2021","journal-title":"Cell"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ni.3045","article-title":"Respiratory epithelial cells orchestrate pulmonary innate immunity","volume":"16","author":"J A Whitsett","year":"2015","journal-title":"Nat Immunol"},{"issue":"10","key":"ref6","doi-asserted-by":"crossref","first-page":"e25333","DOI":"10.1371\/journal.pone.0025333","article-title":"Antiviral activity and increased host defense against influenza infection elicited by the human cathelicidin LL-37","volume":"6","author":"P G Barlow","year":"2011","journal-title":"PLoS One"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"e73659","DOI":"10.1371\/journal.pone.0073659","article-title":"The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus","volume":"8","author":"S M Currie","year":"2013","journal-title":"PLoS One"},{"issue":"24","key":"ref8","doi-asserted-by":"crossref","first-page":"4965","DOI":"10.1016\/j.jmb.2013.09.038","article-title":"Antiviral mechanisms of human defensins","volume":"425","author":"S S Wilson","year":"2013","journal-title":"J Mol Biol"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12985-018-1035-2","article-title":"Human \u03b2-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity","volume":"15","author":"J Kim","year":"2018","journal-title":"Virol J"},{"issue":"14","key":"ref10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21144903","article-title":"Lactoferrin as protective natural barrier of respiratory and intestinal mucosa against coronavirus infection and inflammation","volume":"21","author":"E Campione","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"622598","DOI":"10.3389\/fimmu.2020.622598","article-title":"SP-A and SP-D: dual functioning immune molecules with antiviral and immunomodulatory properties","volume":"11","author":"A Watson","year":"2021","journal-title":"Front Immunol"},{"issue":"05","key":"ref12","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.immuni.2017.04.025","article-title":"Interferon-\u03bb mediates non-redundant front-line antiviral protection against influenza virus infection without compromising host fitness","volume":"46","author":"I E Galani","year":"2017","journal-title":"Immunity"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nri3600","article-title":"Alveolar macrophages: plasticity in a tissue-specific context","volume":"14","author":"T Hussell","year":"2014","journal-title":"Nat Rev Immunol"},{"issue":"07","key":"ref14","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1002\/eji.201344359","article-title":"Transient ablation of alveolar macrophages leads to massive pathology of influenza infection without affecting cellular adaptive immunity","volume":"44","author":"C Purnama","year":"2014","journal-title":"Eur J Immunol"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"e1004053","DOI":"10.1371\/journal.ppat.1004053","article-title":"Alveolar macrophages are essential for protection from respiratory failure and associated morbidity following influenza virus infection","volume":"10","author":"C Schneider","year":"2014","journal-title":"PLoS Pathog"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"e1006140","DOI":"10.1371\/journal.ppat.1006140","article-title":"Alveolar macrophages prevent lethal influenza pneumonia by inhibiting infection of type-1 alveolar epithelial cells","volume":"13","author":"A Cardani","year":"2017","journal-title":"PLoS Pathog"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201012-2036OC","article-title":"GM-CSF in the lung protects against lethal influenza infection","volume":"184","author":"F-F Huang","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"issue":"16","key":"ref18","doi-asserted-by":"crossref","first-page":"e105057","DOI":"10.15252\/embj.2020105057","article-title":"Alveolar macrophage-derived extracellular vesicles inhibit endosomal fusion of influenza virus","volume":"39","author":"D J Schneider","year":"2020","journal-title":"EMBO J"},{"issue":"04","key":"ref19","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.immuni.2021.03.010","article-title":"Overlapping and distinct features of viral and allergen immunity in the human lung","volume":"54","author":"J A Harker","year":"2021","journal-title":"Immunity"},{"issue":"11","key":"ref20","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.4049\/jimmunol.1100987","article-title":"Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells","volume":"187","author":"A WS Ho","year":"2011","journal-title":"J Immunol"},{"issue":"05","key":"ref21","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1084\/jem.20052359","article-title":"Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus","volume":"203","author":"J J Smit","year":"2006","journal-title":"J Exp Med"},{"issue":"02","key":"ref22","doi-asserted-by":"crossref","first-page":"871","DOI":"10.4049\/jimmunol.182.2.871","article-title":"Plasmacytoid dendritic cells are dispensable during primary influenza virus infection","volume":"182","author":"A I Wolf","year":"2009","journal-title":"J Immunol"},{"issue":"06","key":"ref23","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1164\/rccm.201507-1376OC","article-title":"Flow cytometric analysis of mononuclear phagocytes in nondiseased human lung and lung-draining lymph nodes","volume":"193","author":"A N Desch","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"issue":"02","key":"ref24","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/eji.201646523","article-title":"Monocyte-derived dendritic cells enhance protection against secondary influenza challenge by controlling the switch in CD8+ T-cell immunodominance","volume":"47","author":"J LG Cruz","year":"2017","journal-title":"Eur J Immunol"},{"issue":"03","key":"ref25","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1152\/physrev.00032.2017","article-title":"Integrative physiology of pneumonia","volume":"98","author":"L J Quinton","year":"2018","journal-title":"Physiol Rev"},{"issue":"04","key":"ref26","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41385-021-00397-4","article-title":"Neutrophils in respiratory viral infections","volume":"14","author":"C Johansson","year":"2021","journal-title":"Mucosal Immunol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"aaa4352","DOI":"10.1126\/science.aaa4352","article-title":"Neutrophil trails guide influenza-specific CD8+ T cells in the airways","volume":"349","author":"K Lim","year":"2015","journal-title":"Science"},{"issue":"09","key":"ref28","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/s41590-020-0746-x","article-title":"In situ neutrophil efferocytosis shapes T cell immunity to influenza infection","volume":"21","author":"K Lim","year":"2020","journal-title":"Nat Immunol"},{"issue":"03","key":"ref29","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/icb.2016.97","article-title":"The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis","volume":"95","author":"M Duan","year":"2017","journal-title":"Immunol Cell Biol"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2013.06.013","article-title":"A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection","volume":"154","author":"M Brandes","year":"2013","journal-title":"Cell"},{"issue":"02","key":"ref31","doi-asserted-by":"crossref","first-page":"e1001304","DOI":"10.1371\/journal.ppat.1001304","article-title":"Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice","volume":"7","author":"S U Seo","year":"2011","journal-title":"PLoS Pathog"},{"issue":"05","key":"ref32","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1084\/jem.20140825","article-title":"Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes","volume":"212","author":"M Goritzka","year":"2015","journal-title":"J Exp Med"},{"issue":"05","key":"ref33","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.4049\/jimmunol.1200168","article-title":"Rapid differentiation of monocytes into type I IFN-producing myeloid dendritic cells as an antiviral strategy against influenza virus infection","volume":"189","author":"W Cao","year":"2012","journal-title":"J Immunol"},{"issue":"04","key":"ref34","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.4049\/jimmunol.180.4.2562","article-title":"CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality","volume":"180","author":"K L Lin","year":"2008","journal-title":"J Immunol"},{"issue":"03","key":"ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/v11030243","article-title":"Viral infection of human natural killer cells","volume":"11","author":"E A van Erp","year":"2019","journal-title":"Viruses"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.3389\/fimmu.2018.02061","article-title":"The dual nature of type I and type II interferons","volume":"9","author":"A J Lee","year":"2018","journal-title":"Front Immunol"},{"issue":"06","key":"ref37","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1016\/j.ajpath.2011.09.003","article-title":"Negative regulation of lung inflammation and immunopathology by TNF-\u03b1 during acute influenza infection","volume":"179","author":"D Damjanovic","year":"2011","journal-title":"Am J Pathol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev.immunol.17.1.189","article-title":"Natural killer cells in antiviral defense: function and regulation by innate cytokines","volume":"17","author":"C A Biron","year":"1999","journal-title":"Annu Rev Immunol"},{"issue":"04","key":"ref39","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mad.2008.01.003","article-title":"Characterization of age-related changes in natural killer cells during primary influenza infection in mice","volume":"129","author":"S Nogusa","year":"2008","journal-title":"Mech Ageing Dev"},{"issue":"08","key":"ref40","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.4049\/jimmunol.1001758","article-title":"NK cell deficiency predisposes to viral-induced Th2-type allergic inflammation via epithelial-derived IL-25","volume":"185","author":"G E Kaiko","year":"2010","journal-title":"J Immunol"},{"issue":"02","key":"ref41","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/infdis\/jis340","article-title":"Critical role of natural killer cells in lung immunopathology during influenza infection in mice","volume":"206","author":"M F Abdul-Careem","year":"2012","journal-title":"J Infect Dis"},{"issue":"04","key":"ref42","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/JVI.06209-11","article-title":"Natural killer cells are involved in acute lung immune injury caused by respiratory syncytial virus infection","volume":"86","author":"F Li","year":"2012","journal-title":"J Virol"},{"issue":"04","key":"ref43","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1002\/eji.201242620","article-title":"NK cells exacerbate the pathology of influenza virus infection in mice","volume":"43","author":"G Zhou","year":"2013","journal-title":"Eur J Immunol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1126\/science.aac9593","article-title":"Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs","volume":"350","author":"G Gasteiger","year":"2015","journal-title":"Science"},{"issue":"07","key":"ref45","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ni.2045","article-title":"Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity","volume":"12","author":"Y J Chang","year":"2011","journal-title":"Nat Immunol"},{"issue":"10","key":"ref46","doi-asserted-by":"crossref","first-page":"e1005217","DOI":"10.1371\/journal.ppat.1005217","article-title":"Respiratory syncytial virus disease is mediated by age-variable IL-33","volume":"11","author":"J Saravia","year":"2015","journal-title":"PLoS Pathog"},{"issue":"04","key":"ref47","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.4049\/jimmunol.1700216","article-title":"The innate cytokines IL-25, IL-33, and TSLP cooperate in the induction of type 2 innate lymphoid cell expansion and mucous metaplasia in rhinovirus-infected immature mice","volume":"199","author":"M Han","year":"2017","journal-title":"J Immunol"},{"issue":"01","key":"ref48","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/ni.3308","article-title":"Type I interferon restricts type 2 immunopathology through the regulation of group 2 innate lymphoid cells","volume":"17","author":"C U Duerr","year":"2016","journal-title":"Nat Immunol"},{"issue":"08","key":"ref49","first-page":"2001","article-title":"IL-1\u03b2 prevents ILC2 expansion, type 2 cytokine secretion, and mucus metaplasia in response to early-life rhinovirus infection in mice","volume":"75","author":"M Han","year":"2020","journal-title":"Allergy Eur J Allergy Clin Immunol"},{"issue":"07","key":"ref50","doi-asserted-by":"crossref","first-page":"e1008651","DOI":"10.1371\/journal.ppat.1008651","article-title":"HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling","volume":"16","author":"Z Loh","year":"2020","journal-title":"PLoS Pathog"},{"issue":"01","key":"ref51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/mi.2017.41","article-title":"IFN-\u03b3 increases susceptibility to influenza A infection through suppression of group II innate lymphoid cells","volume":"11","author":"D Califano","year":"2018","journal-title":"Mucosal Immunol"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"510","DOI":"10.4049\/jimmunol.1601984","article-title":"STAT1 represses cytokine-producing group 2 and group 3 innate lymphoid cells during viral infection","volume":"199","author":"M T Stier","year":"2017","journal-title":"J Immunol"},{"issue":"11","key":"ref53","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1164\/rccm.201812-2366OC","article-title":"Elevated levels of type 2 respiratory innate lymphoid cells in human infants with severe respiratory syncytial virus bronchiolitis","volume":"200","author":"L D Vu","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"580679","DOI":"10.3389\/fcimb.2021.580679","article-title":"Divergent mast cell responses modulate antiviral immunity during influenza virus infection","volume":"11","author":"A R Murphy-Schafer","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"issue":"02","key":"ref55","doi-asserted-by":"crossref","first-page":"161","DOI":"10.3390\/v13020161","article-title":"Interactions of influenza and SARS-CoV-2 with the lung endothelium: similarities, differences, and implications for therapy","volume":"13","author":"E Latreille","year":"2021","journal-title":"Viruses"},{"issue":"08","key":"ref56","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.4049\/jimmunol.1600787","article-title":"Eosinophils promote antiviral immunity in mice infected with influenza A virus","volume":"198","author":"A E Samarasinghe","year":"2017","journal-title":"J Immunol"},{"issue":"03","key":"ref57","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3390\/cells10030509","article-title":"Eosinophil responses at the airway epithelial barrier during the early phase of influenza A virus infection in C57BL\/6 mice","volume":"10","author":"M Tiwary","year":"2021","journal-title":"Cells"},{"issue":"01","key":"ref58","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s12985-020-01449-0","article-title":"Role of \u03b3\u03b4 T cells in controlling viral infections with a focus on influenza virus: implications for designing novel therapeutic approaches","volume":"17","author":"A Sabbaghi","year":"2020","journal-title":"Virol J"},{"issue":"05","key":"ref59","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.immuni.2017.10.009","article-title":"CD4+ T cell help confers a cytotoxic T cell effector program including coinhibitory receptor downregulation and increased tissue invasiveness","volume":"47","author":"T Ahrends","year":"2017","journal-title":"Immunity"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.3389\/fimmu.2018.03043","article-title":"Type 1 conventional CD103+ dendritic cells control effector CD8+ T cell migration, survival, and memory responses during influenza infection","volume":"9","author":"S L Ng","year":"2018","journal-title":"Front Immunol"},{"issue":"08","key":"ref61","doi-asserted-by":"crossref","first-page":"E730","DOI":"10.3390\/v11080730","article-title":"Plasmacytoid dendritic cells contribute to the production of ifn-\u03b2 via tlr7-myd88-dependent pathway and ctl priming during respiratory syncytial virus infection","volume":"11","author":"T H Kim","year":"2019","journal-title":"Viruses"},{"issue":"04","key":"ref62","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nri3166","article-title":"Regulating the adaptive immune response to respiratory virus infection","volume":"12","author":"T J Braciale","year":"2012","journal-title":"Nat Rev Immunol"},{"issue":"03","key":"ref63","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nm.1929","article-title":"Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10","volume":"15","author":"J Sun","year":"2009","journal-title":"Nat Med"},{"issue":"12","key":"ref64","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1002\/eji.201646548","article-title":"Type I IFN signaling facilitates the development of IL-10-producing effector CD8+ T cells during murine influenza virus infection","volume":"46","author":"L Jiang","year":"2016","journal-title":"Eur J Immunol"},{"issue":"04","key":"ref65","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ni.1996","article-title":"CD4+ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs","volume":"12","author":"J Sun","year":"2011","journal-title":"Nat Immunol"},{"issue":"06","key":"ref66","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.4049\/jimmunol.1100764","article-title":"Multiple CD4+ T cell subsets produce immunomodulatory IL-10 during respiratory syncytial virus infection","volume":"187","author":"K A Weiss","year":"2011","journal-title":"J Immunol"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.3389\/fimmu.2019.02351","article-title":"Kinetics and Phenotype of the CD4 T Cell Response to Influenza Virus Infections","volume":"10","author":"E E Hornick","year":"2019","journal-title":"Front Immunol"},{"issue":"12","key":"ref68","doi-asserted-by":"crossref","first-page":"6792","DOI":"10.1128\/JVI.07172-11","article-title":"Multifunctional CD4 cells expressing gamma interferon and perforin mediate protection against lethal influenza virus infection","volume":"86","author":"D M Brown","year":"2012","journal-title":"J Virol"},{"issue":"02","key":"ref69","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nm.2612","article-title":"Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans","volume":"18","author":"T M Wilkinson","year":"2012","journal-title":"Nat Med"},{"issue":"03","key":"ref70","doi-asserted-by":"crossref","first-page":"a038729","DOI":"10.1101\/cshperspect.a038729","article-title":"Immunity to influenza infection in humans","volume":"11","author":"D J Topham","year":"2021","journal-title":"Cold Spring Harb Perspect Med"},{"issue":"05","key":"ref71","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1128\/JVI.05685-11","article-title":"Influenza A virus infection results in a robust, antigen-responsive, and widely disseminated Foxp3+ regulatory T cell response","volume":"86","author":"R J Betts","year":"2012","journal-title":"J Virol"},{"issue":"05","key":"ref72","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.cell.2015.08.021","article-title":"A distinct function of regulatory T cells in tissue protection","volume":"162","author":"N Arpaia","year":"2015","journal-title":"Cell"},{"issue":"04","key":"ref73","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.4049\/jimmunol.1800096","article-title":"CD4+ regulatory T cells exert differential functions during early and late stages of the immune response to respiratory viruses","volume":"201","author":"M C Rogers","year":"2018","journal-title":"J Immunol"},{"issue":"20","key":"ref74","doi-asserted-by":"crossref","first-page":"10946","DOI":"10.1128\/JVI.01295-13","article-title":"Regulatory T cells prevent Th2 immune responses and pulmonary eosinophilia during respiratory syncytial virus infection in mice","volume":"87","author":"L R Durant","year":"2013","journal-title":"J Virol"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.05.045","article-title":"Loss of regulatory capacity in T regulatory cells upon rhinovirus infection","author":"K Jansen","year":"2021","journal-title":"J Allergy Clin Immunol"},{"issue":"01","key":"ref76","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ni.3056","article-title":"Antiviral B cell and T cell immunity in the lungs","volume":"16","author":"C Chiu","year":"2015","journal-title":"Nat Immunol"},{"issue":"07","key":"ref77","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.4049\/jimmunol.176.7.4343","article-title":"Type I IFN receptor signals directly stimulate local B cells early following influenza virus infection","volume":"176","author":"E S Coro","year":"2006","journal-title":"J Immunol"},{"issue":"02","key":"ref78","doi-asserted-by":"crossref","first-page":"351","DOI":"10.4049\/jimmunol.1801208","article-title":"The multifaceted B cell response to influenza virus","volume":"202","author":"J H Lam","year":"2019","journal-title":"J Immunol"},{"issue":"13","key":"ref79","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.1084\/jem.20080979","article-title":"Dual role for B-1a cells in immunity to influenza virus infection","volume":"205","author":"Y S Choi","year":"2008","journal-title":"J Exp Med"},{"issue":"05","key":"ref80","doi-asserted-by":"crossref","first-page":"E504","DOI":"10.3390\/v12050504","article-title":"Host protective immune responses against influenza a virus infection","volume":"12","author":"H E Jung","year":"2020","journal-title":"Viruses"},{"issue":"01","key":"ref81","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41467-017-00928-3","article-title":"Alveolar macrophages are critical for broadly-reactive antibody-mediated protection against influenza A virus in mice","volume":"8","author":"W He","year":"2017","journal-title":"Nat Commun"},{"issue":"07","key":"ref82","doi-asserted-by":"crossref","first-page":"e1009708","DOI":"10.1371\/journal.ppat.1009708","article-title":"Antibody-independent functions of B cells during viral infections","volume":"17","author":"V Upasani","year":"2021","journal-title":"PLoS Pathog"},{"issue":"01","key":"ref83","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.chom.2018.12.006","article-title":"Innate and adaptive immune memory: an evolutionary continuum in the host's response to pathogens","volume":"25","author":"M G Netea","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"02","key":"ref84","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.immuni.2018.01.007","article-title":"Human T cell development, localization, and function throughout life","volume":"48","author":"B V Kumar","year":"2018","journal-title":"Immunity"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"6833","DOI":"10.1038\/ncomms7833","article-title":"Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8+ T cells","volume":"6","author":"Z Wang","year":"2015","journal-title":"Nat Commun"},{"issue":"05","key":"ref86","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.immuni.2020.09.005","article-title":"Central memory CD8+ T cells derive from stem-like Tcf7hi effector cells in the absence of cytotoxic differentiation","volume":"53","author":"D Pais Ferreira","year":"2020","journal-title":"Immunity"},{"issue":"01","key":"ref87","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"L Gattinoni","year":"2017","journal-title":"Nat Med"},{"issue":"01","key":"ref88","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.immuni.2014.05.018","article-title":"Serial transfer of single-cell-derived immunocompetence reveals stemness of CD8(+) central memory T cells","volume":"41","author":"P Graef","year":"2014","journal-title":"Immunity"},{"issue":"317","key":"ref89","doi-asserted-by":"crossref","first-page":"317ra198","DOI":"10.1126\/scitranslmed.aac8265","article-title":"Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory","volume":"7","author":"G Oliveira","year":"2015","journal-title":"Sci Transl Med"},{"issue":"01","key":"ref90","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.immuni.2008.05.011","article-title":"The chemokine receptor CCR5 plays a key role in the early memory CD8+ T cell response to respiratory virus infections","volume":"29","author":"J E Kohlmeier","year":"2008","journal-title":"Immunity"},{"issue":"10","key":"ref91","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1038\/nm.3350","article-title":"Cellular immune correlates of protection against symptomatic pandemic influenza","volume":"19","author":"S Sridhar","year":"2013","journal-title":"Nat Med"},{"issue":"12","key":"ref92","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1038\/ni.3589","article-title":"Programs for the persistence, vigilance and control of human CD8+ lung-resident memory T cells","volume":"17","author":"P Hombrink","year":"2016","journal-title":"Nat Immunol"},{"issue":"12","key":"ref93","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1016\/j.celrep.2017.08.078","article-title":"Human tissue-resident memory T cells are defined by core transcriptional and functional signatures in lymphoid and mucosal sites","volume":"20","author":"B V Kumar","year":"2017","journal-title":"Cell Rep"},{"issue":"03","key":"ref94","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/mi.2013.67","article-title":"Lung niches for the generation and maintenance of tissue-resident memory T cells","volume":"7","author":"D L Turner","year":"2014","journal-title":"Mucosal Immunol"},{"issue":"04","key":"ref95","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/s41385-018-0003-x","article-title":"Pulmonary antigen encounter regulates the establishment of tissue-resident CD8 memory T cells in the lung airways and parenchyma","volume":"11","author":"S R McMaster","year":"2018","journal-title":"Mucosal Immunol"},{"issue":"05","key":"ref96","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.4049\/jimmunol.1402369","article-title":"Smad4 promotes differentiation of effector and circulating memory CD8 T cells but is dispensable for tissue-resident memory CD8 T cells","volume":"194","author":"Y Hu","year":"2015","journal-title":"J Immunol"},{"issue":"01","key":"ref97","doi-asserted-by":"crossref","first-page":"203","DOI":"10.4049\/jimmunol.1402975","article-title":"Airway-resident memory CD8 T cells provide antigen-specific protection against respiratory virus challenge through rapid IFN-\u03b3 production","volume":"195","author":"S R McMaster","year":"2015","journal-title":"J Immunol"},{"issue":"12","key":"ref98","doi-asserted-by":"crossref","first-page":"eaam6970","DOI":"10.1126\/sciimmunol.aam6970","article-title":"Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection","volume":"2","author":"A Pizzolla","year":"2017","journal-title":"Sci Immunol"},{"issue":"01","key":"ref99","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41385-020-0309-3","article-title":"Long-term maintenance of lung resident memory T cells is mediated by persistent antigen","volume":"14","author":"I Uddb\u00e4ck","year":"2021","journal-title":"Mucosal Immunol"},{"issue":"07","key":"ref100","doi-asserted-by":"crossref","first-page":"eaag2031","DOI":"10.1126\/sciimmunol.aag2031","article-title":"Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity","volume":"2","author":"B Sl\u00fctter","year":"2017","journal-title":"Sci Immunol"},{"issue":"03","key":"ref101","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41590-019-0584-x","article-title":"Environmental cues regulate epigenetic reprogramming of airway-resident memory CD8+ T cells","volume":"21","author":"S L Hayward","year":"2020","journal-title":"Nat Immunol"},{"issue":"02","key":"ref102","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1189\/jlb.0313180","article-title":"Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection","volume":"95","author":"T Wu","year":"2014","journal-title":"J Leukoc Biol"},{"issue":"06","key":"ref103","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/s41577-019-0143-6","article-title":"The human antibody response to influenza A virus infection and vaccination","volume":"19","author":"F Krammer","year":"2019","journal-title":"Nat Rev Immunol"},{"issue":"04","key":"ref104","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.immuni.2018.03.027","article-title":"T follicular helper cell-germinal center B cell interaction strength regulates entry into plasma cell or recycling germinal center cell fate","volume":"48","author":"W Ise","year":"2018","journal-title":"Immunity"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-immunol-020711-075032","article-title":"Germinal centers","volume":"30","author":"G D Victora","year":"2012","journal-title":"Annu Rev Immunol"},{"issue":"01","key":"ref106","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1038\/s41467-021-23018-x","article-title":"Immune cellular networks underlying recovery from influenza virus infection in acute hospitalized patients","volume":"12","author":"T HO Nguyen","year":"2021","journal-title":"Nat Commun"},{"issue":"01","key":"ref107","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/imr.12640","article-title":"Generation of memory B cells and their reactivation","volume":"283","author":"T Inoue","year":"2018","journal-title":"Immunol Rev"},{"issue":"01","key":"ref108","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41590-018-0260-6","article-title":"The establishment of resident memory B cells in the lung requires local antigen encounter","volume":"20","author":"S R Allie","year":"2019","journal-title":"Nat Immunol"},{"issue":"07","key":"ref109","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1073\/pnas.1115369109","article-title":"Memory B cells in the lung participate in protective humoral immune responses to pulmonary influenza virus reinfection","volume":"109","author":"T Onodera","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"03","key":"ref110","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/nri3802","article-title":"Memory B cells","volume":"15","author":"T Kurosaki","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3389\/fmicb.2017.00900","article-title":"Nasal IgA provides protection against human influenza challenge in volunteers with low serum influenza antibody titre","volume":"8","author":"V MW Gould","year":"2017","journal-title":"Front Microbiol"},{"issue":"09","key":"ref112","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1164\/rccm.201412-2256OC","article-title":"Impaired antibody-mediated protection and defective IgA B-cell memory in experimental infection of adults with respiratory syncytial virus","volume":"191","author":"M S Habibi","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"06","key":"ref113","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"M G Netea","year":"2020","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"ref114","doi-asserted-by":"crossref","first-page":"e00165-21","DOI":"10.1128\/JVI.00165-21","article-title":"Phenotypic and functional characteristics of a novel influenza virus hemagglutinin-specific memory NK cell","volume":"95","author":"J Zheng","year":"2021","journal-title":"J Virol"},{"issue":"03","key":"ref115","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1378\/chest.10-1396","article-title":"Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus","volume":"139","author":"I Mart\u00edn-Loeches","year":"2011","journal-title":"Chest"},{"issue":"03","key":"ref116","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.amjmed.2004.09.016","article-title":"Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation","volume":"118","author":"T R Talbot","year":"2005","journal-title":"Am J Med"},{"issue":"07","key":"ref117","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1086\/591708","article-title":"Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness","volume":"198","author":"D M Morens","year":"2008","journal-title":"J Infect Dis"},{"issue":"04","key":"ref118","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrmicro3231","article-title":"The co-pathogenesis of influenza viruses with bacteria in the lung","volume":"12","author":"J A McCullers","year":"2014","journal-title":"Nat Rev Microbiol"},{"issue":"10","key":"ref119","doi-asserted-by":"crossref","first-page":"3764","DOI":"10.1128\/IAI.00298-15","article-title":"Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease","volume":"83","author":"A Rynda-Apple","year":"2015","journal-title":"Infect Immun"},{"issue":"09","key":"ref120","doi-asserted-by":"crossref","first-page":"e41879","DOI":"10.1371\/journal.pone.0041879","article-title":"Poly I:C enhances susceptibility to secondary pulmonary infections by gram-positive bacteria","volume":"7","author":"X Tian","year":"2012","journal-title":"PLoS One"},{"issue":"04","key":"ref121","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1165\/rcmb.2007-0417OC","article-title":"Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae","volume":"42","author":"L A Pittet","year":"2010","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"03","key":"ref122","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1183\/13993003.01282-2015","article-title":"Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions","volume":"47","author":"K R Short","year":"2016","journal-title":"Eur Respir J"},{"issue":"12","key":"ref123","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1164\/rccm.200801-136OC","article-title":"Rhinovirus disrupts the barrier function of polarized airway epithelial cells","volume":"178","author":"U Sajjan","year":"2008","journal-title":"Am J Respir Crit Care Med"},{"issue":"01","key":"ref124","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.chom.2014.06.005","article-title":"Influenza promotes pneumococcal growth during coinfection by providing host sialylated substrates as a nutrient source","volume":"16","author":"S J Siegel","year":"2014","journal-title":"Cell Host Microbe"},{"issue":"49","key":"ref125","doi-asserted-by":"crossref","first-page":"31386","DOI":"10.1073\/pnas.2012265117","article-title":"Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways","volume":"117","author":"V Sender","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"05","key":"ref126","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nm1765","article-title":"Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection","volume":"14","author":"K Sun","year":"2008","journal-title":"Nat Med"},{"issue":"06","key":"ref127","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.4049\/jimmunol.2000094","article-title":"Influenza infection induces alveolar macrophage dysfunction and thereby enables noninvasive Streptococcus pneumoniae to cause deadly pneumonia","volume":"205","author":"A K Verma","year":"2020","journal-title":"J Immunol"},{"issue":"01","key":"ref128","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cell.2020.08.020","article-title":"Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis","volume":"183","author":"A S Neupane","year":"2020","journal-title":"Cell"},{"issue":"04","key":"ref129","doi-asserted-by":"crossref","first-page":"e01335-19","DOI":"10.1128\/mBio.01335-19","article-title":"Allergic airway disease prevents lethal synergy of influenza A virus-streptococcus pneumoniae coinfection","volume":"10","author":"S Roberts","year":"2019","journal-title":"MBio"},{"issue":"01","key":"ref130","first-page":"1","article-title":"Loss of T-bet confers survival advantage to influenza-bacterial superinfection","volume":"38","author":"J Z Er","year":"2019","journal-title":"EMBO J"},{"issue":"12","key":"ref131","doi-asserted-by":"crossref","first-page":"101767","DOI":"10.1016\/j.isci.2020.101767","article-title":"Flu virus attenuates memory clearance of Pneumococcus via IFN-\u03b3-dependent Th17 and independent antibody mechanisms","volume":"23","author":"N Li","year":"2020","journal-title":"iScience"}],"container-title":["Seminars in Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0041-1736459.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T01:13:17Z","timestamp":1639703597000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0041-1736459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":131,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2021,12,16]]},"published-print":{"date-parts":[[2021,12]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0041-1736459","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1069-3424","1098-9048"],"issn-type":[{"value":"1069-3424","type":"print"},{"value":"1098-9048","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]}}}