{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:23:25Z","timestamp":1768469005728,"version":"3.49.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T00:00:00Z","timestamp":1550793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R56 AI125324"],"award-info":[{"award-number":["R56 AI125324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K25 AI00946"],"award-info":[{"award-number":["K25 AI00946"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012524","name":"American Lebanese Syrian Associated Charities","doi-asserted-by":"publisher","award":["JAM"],"award-info":[{"award-number":["JAM"]}],"id":[{"id":"10.13039\/100012524","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010923","name":"Missouri State University","doi-asserted-by":"publisher","award":["F07314"],"award-info":[{"award-number":["F07314"]}],"id":[{"id":"10.13039\/100010923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0212236","type":"journal-article","created":{"date-parts":[[2019,2,22]],"date-time":"2019-02-22T18:48:22Z","timestamp":1550861302000},"page":"e0212236","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Enhanced IL-1\u03b2 production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7237-6002","authenticated-orcid":true,"given":"Angeline E.","family":"Rodriguez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Bogart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan A.","family":"McCullers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thirumala-Devi","family":"Kanneganti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6586-004X","authenticated-orcid":true,"given":"Christopher R.","family":"Lupfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2019,2,22]]},"reference":[{"issue":"13","key":"ref1","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2169\/internalmedicine.46.6364","article-title":"Disease severity in patients with simultaneous influenza and bacterial pneumonia","volume":"46","author":"M Seki","year":"2007","journal-title":"Internal medicine (Tokyo, Japan)"},{"issue":"5","key":"ref2","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1093\/infdis\/jit473","article-title":"Complications and associated bacterial coinfections among children hospitalized with seasonal or pandemic influenza, United States, 2003\u20132010","volume":"209","author":"FS Dawood","year":"2014","journal-title":"J Infect Dis"},{"issue":"5","key":"ref3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1086\/313772","article-title":"Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection","volume":"30","author":"KL O\u2019Brien","year":"2000","journal-title":"Clin Infect Dis"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.coi.2015.02.002","article-title":"The immunology of influenza virus-associated bacterial pneumonia","volume":"34","author":"KM Robinson","year":"2015","journal-title":"Curr Opin Immunol"},{"issue":"4","key":"ref5","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":"JA McCullers","year":"2014","journal-title":"Nat Rev Microbiol"},{"issue":"10","key":"ref6","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"},{"key":"ref7","first-page":"327","article-title":"Secondary bacterial infections in influenza virus infection pathogenesis","volume":"385","author":"AM Smith","year":"2014","journal-title":"Curr Top Microbiol Immunol"},{"issue":"5","key":"ref8","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4049\/jimmunol.1301152","article-title":"Immune dysfunction and bacterial coinfections following influenza","volume":"191","author":"DW Metzger","year":"2013","journal-title":"J Immunol"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1086\/341462","article-title":"Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor","volume":"186","author":"JA McCullers","year":"2002","journal-title":"J Infect Dis"},{"issue":"4","key":"ref10","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":"LA Pittet","year":"2010","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"3","key":"ref11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.ppat.1003238","article-title":"Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae","volume":"9","author":"AM Smith","year":"2013","journal-title":"PLoS Pathogens"},{"issue":"3","key":"ref12","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.4049\/jimmunol.1300014","article-title":"Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections","volume":"191","author":"HE Ghoneim","year":"2013","journal-title":"J Immunol"},{"issue":"8","key":"ref13","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.4049\/jimmunol.154.8.3952","article-title":"Neutrophil deactivation by influenza A virus. Role of hemagglutinin binding to specific sialic acid-bearing cellular proteins","volume":"154","author":"KL Hartshorn","year":"1995","journal-title":"J Immunol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"38703","DOI":"10.1038\/srep38703","article-title":"A Critical, Nonlinear Threshold Dictates Bacterial Invasion and Initial Kinetics During Influenza","volume":"6","author":"AM Smith","year":"2016","journal-title":"Sci Rep"},{"issue":"1 Suppl","key":"ref15","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1097\/01.inf.0000108197.81270.35","article-title":"Respiratory viruses predisposing to bacterial infections: role of neuraminidase","volume":"23","author":"VT Peltola","year":"2004","journal-title":"Pediatr Infect Dis J"},{"issue":"7","key":"ref16","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1182\/blood.V93.7.2395","article-title":"Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria","volume":"93","author":"ML Colamussi","year":"1999","journal-title":"Blood"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"6707","DOI":"10.1128\/IAI.00789-06","article-title":"Both Influenza-Induced Neutrophil Dysfunction and Neutrophil-Independent Mechanisms Contribute to Increased Susceptibility to a Secondary Streptococcus pneumoniae Infection","volume":"74","author":"A Lynnelle","year":"2006","journal-title":"Infection and Immunity"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1189\/jlb.69.1.50","article-title":"Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae: role of respiratory burst","volume":"69","author":"G Engelich","year":"2001","journal-title":"Journal of Leukocyte Biology"},{"issue":"12","key":"ref19","doi-asserted-by":"crossref","first-page":"7603","DOI":"10.4049\/jimmunol.172.12.7603","article-title":"IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection","volume":"172","author":"KF van der Sluijs","year":"2004","journal-title":"J Immunol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1183\/09031936.04.00126103","article-title":"Immunokinetics in severe pneumonia due to influenza virus and bacteria coinfection in mice","author":"KY M. Seki","year":"2004","journal-title":"European Respiratory Journal"},{"issue":"1","key":"ref21","first-page":"82","article-title":"Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza","volume":"57","author":"MW Smith","year":"2007","journal-title":"Comp Med"},{"key":"ref22","article-title":"Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice","author":"A Shahangian","year":"2009","journal-title":"The Journal of Clinical Investigation"},{"issue":"9","key":"ref23","doi-asserted-by":"crossref","first-page":"3657","DOI":"10.1172\/JCI57762","article-title":"Synergistic stimulation of type I interferons during influenza virus coinfection promotes Streptococcus pneumoniae colonization in mice","volume":"121","author":"S Nakamura","year":"2011","journal-title":"Journal of Clinical Investigation"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.4049\/jimmunol.1002194","article-title":"Influenza A inhibits Th17-mediated host defense against bacterial pneumonia in mice","volume":"186","author":"A Kudva","year":"2011","journal-title":"J Immunol"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"L158","DOI":"10.1152\/ajplung.00338.2014","article-title":"Influenza-induced type I interferon enhances susceptibility to gram-negative and gram-positive bacterial pneumonia in mice","volume":"309","author":"B Lee","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4049\/jimmunol.1701406","article-title":"Effects of Influenza on Alveolar Macrophage Viability Are Dependent on Mouse Genetic Strain","volume":"201","author":"D Califano","year":"2018","journal-title":"J Immunol"},{"issue":"5","key":"ref27","first-page":"778","article-title":"Immune impairment of alveolar macrophage phagocytosis during influenza virus pneumonia","volume":"126","author":"GJ Jakab","year":"1982","journal-title":"Am Rev Respir Dis"},{"issue":"6","key":"ref28","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1089\/jir.2014.0087","article-title":"Dynamics of Increasing IFN-gamma Exposure on Murine MH-S Cell-Line Alveolar Macrophage Phagocytosis of Streptococcus pneumoniae","volume":"35","author":"MJ Mina","year":"2015","journal-title":"J Interferon Cytokine Res"},{"issue":"5","key":"ref29","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":"1","key":"ref30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.5492\/wjccm.v5.i1.89","article-title":"Corticosteroids for severe influenza pneumonia: A critical appraisal","volume":"5","author":"WL Nedel","year":"2016","journal-title":"World J Crit Care Med"},{"issue":"9","key":"ref31","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/infdis\/jit653","article-title":"Adjunctive corticosteroid therapy improves lung immunopathology and survival during severe secondary pneumococcal pneumonia in mice","volume":"209","author":"HE Ghoneim","year":"2014","journal-title":"J Infect Dis"},{"key":"ref32","article-title":"Role of Corticosteroids in Influenza Pneumonia (H1N1) Patients","author":"K Karunanithi","year":"2017","journal-title":"Universal Journal of Medical Science"},{"issue":"4","key":"ref33","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1093\/cid\/cir398","article-title":"Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1 infection","volume":"53","author":"K Han","year":"2011","journal-title":"Clin Infect Dis"},{"issue":"2","key":"ref34","article-title":"Lethal Synergism between Influenza and Streptococcus pneumoniae","volume":"2","author":"JM Rudd","year":"2016","journal-title":"J Infect Pulm Dis"},{"issue":"2","key":"ref35","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","article-title":"The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta","volume":"10","author":"F Martinon","year":"2002","journal-title":"Mol Cell"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2009.02.006","article-title":"The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1","volume":"30","author":"PG Thomas","year":"2009","journal-title":"Immunity"},{"issue":"1","key":"ref37","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1084\/jem.20081667","article-title":"Inflammasome recognition of influenza virus is essential for adaptive immune responses","volume":"206","author":"T Ichinohe","year":"2009","journal-title":"The Journal of experimental medicine"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.immuni.2009.02.005","article-title":"The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA","volume":"30","author":"IC Allen","year":"2009","journal-title":"Immunity"},{"issue":"9","key":"ref39","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.4049\/jimmunol.1100381","article-title":"Critical roles of ASC inflammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection","volume":"187","author":"R Fang","year":"2011","journal-title":"J Immunol"},{"issue":"5","key":"ref40","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/ni.1861","article-title":"Influenza virus activates inflammasomes via its intracellular M2 ion channel","volume":"11","author":"T Ichinohe","year":"2010","journal-title":"Nature immunology"},{"issue":"6","key":"ref41","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1128\/IAI.01572-14","article-title":"Type I interferon signaling regulates activation of the absent in melanoma 2 inflammasome during Streptococcus pneumoniae infection","volume":"82","author":"R Fang","year":"2014","journal-title":"Infect Immun"},{"issue":"7575","key":"ref42","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"J Shi","year":"2015","journal-title":"Nature"},{"issue":"7575","key":"ref43","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"N Kayagaki","year":"2015","journal-title":"Nature"},{"issue":"12","key":"ref44","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/cr.2015.139","article-title":"Gasdermin D is an executor of pyroptosis and required for interleukin-1\u03b2 secretion","volume":"25","author":"WT He","year":"2015","journal-title":"Cell Res"},{"issue":"4","key":"ref45","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.4049\/jimmunol.1700210","article-title":"IL-1 Signaling Prevents Alveolar Macrophage Depletion during Influenza and Streptococcus pneumoniae Coinfection","volume":"200","author":"S Bansal","year":"2018","journal-title":"J Immunol"},{"issue":"10","key":"ref46","doi-asserted-by":"crossref","first-page":"5153","DOI":"10.4049\/jimmunol.1301237","article-title":"Influenza A exacerbates Staphylococcus aureus pneumonia by attenuating IL-1\u03b2 production in mice","volume":"191","author":"KM Robinson","year":"2013","journal-title":"J Immunol"},{"issue":"6877","key":"ref47","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/416194a","article-title":"RICK\/Rip2\/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems","volume":"416","author":"K Kobayashi","year":"2002","journal-title":"Nature"},{"issue":"5633","key":"ref48","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"M Yamamoto","year":"2003","journal-title":"Science"},{"issue":"1","key":"ref49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1083\/jcb.200903124","article-title":"Glyburide inhibits the Cryopyrin\/Nalp3 inflammasome","volume":"187","author":"M Lamkanfi","year":"2009","journal-title":"J Cell Biol"},{"issue":"5","key":"ref50","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/ni.2563","article-title":"Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection","volume":"14","author":"C Lupfer","year":"2013","journal-title":"Nat Immunol"},{"issue":"7","key":"ref51","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1172\/JCI35412","article-title":"Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice","volume":"119","author":"A Shahangian","year":"2009","journal-title":"J Clin Invest"},{"issue":"5","key":"ref52","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1007\/s00705-008-0067-0","article-title":"Inhibition of influenza A H3N8 virus infections in mice by morpholino oligomers","volume":"153","author":"C Lupfer","year":"2008","journal-title":"Arch Virol"},{"issue":"10","key":"ref53","doi-asserted-by":"crossref","first-page":"741","DOI":"10.2105\/AJPH.8.10.741","article-title":"The Use of Convalescent Human Serum in Influenza Pneumonia-a Preliminary Report","volume":"8","author":"LW McGuire","year":"1918","journal-title":"Am J Public Health (N Y)"},{"issue":"1245","key":"ref54","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1126\/science.48.1245.451","article-title":"The Influenza Pneumonia Pandemic in the American Army Camps during September and October. 1918","volume":"48","author":"GA Soper","year":"1918","journal-title":"Science"},{"issue":"8","key":"ref55","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.3201\/eid1408.071313","article-title":"Deaths from bacterial pneumonia during 1918\u201319 influenza pandemic","volume":"14","author":"JF Brundage","year":"2008","journal-title":"Emerging infectious diseases"},{"issue":"7","key":"ref56","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":"DM Morens","year":"2008","journal-title":"J Infect Dis"},{"issue":"8","key":"ref57","doi-asserted-by":"crossref","first-page":"e0182191","DOI":"10.1371\/journal.pone.0182191","article-title":"Influenza virus infections among patients attending emergency department according to main reason to presenting to ED: A 3-year prospective observational study during seasonal epidemic periods","volume":"12","author":"E Casalino","year":"2017","journal-title":"PloS one"},{"issue":"7","key":"ref58","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.97470","article-title":"The inflammasome potentiates influenza\/Staphylococcus aureus superinfection in mice","volume":"3","author":"KM Robinson","year":"2018","journal-title":"JCI Insight"},{"key":"ref59","article-title":"ASC and NLRP3 impair host defense during lethal pneumonia caused by serotype 3 Streptococcus pneumoniae in mice","author":"MHP van Lieshout","year":"2017","journal-title":"European journal of immunology"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0212236","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T22:01:21Z","timestamp":1694642481000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0212236"}},"subtitle":[],"editor":[{"given":"Irving Coy","family":"Allen","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2019,2,22]]},"references-count":59,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,2,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0212236","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,22]]}}}