{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:23:20Z","timestamp":1791195800369,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T00:00:00Z","timestamp":1383264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pneumonia is a leading cause of death worldwide. Staphylococcal aureus can be a cause of severe pneumonia alone or a common pathogen in secondary pneumonia following influenza. Recently, we reported that preceding influenza attenuated the Type 17 pathway, increasing the lung\u2019s susceptibility to secondary infection. IL-1\u03b2 is known to regulate host defense, including playing a role in Th17 polarization. We examined whether IL-1\u03b2 signaling is required for S. aureus host defense and whether influenza infection impacted S. aureus\u2013induced IL-1\u03b2 production and subsequent Type 17 pathway activation. Mice were challenged with S. aureus (USA 300), with or without preceding Influenza A\/PR\/8\/34 H1N1 infection. IL-1R1\u2212\/\u2212 mice had significantly higher S. aureus burden, increased mortality, and decreased Type 17 pathway activation following S. aureus challenge. Coinfected mice had significantly decreased IL-1\u03b2 production versus S. aureus infection alone at early time points following bacterial challenge. Preceding influenza did not attenuate S. aureus\u2013induced inflammasome activation, but there was early suppression of NF-\u03baB activation, suggesting an inhibition of NF-\u03baB\u2013dependent transcription of pro\u2013IL-1\u03b2. Furthermore, overexpression of IL-1\u03b2 in influenza and S. aureus\u2013coinfected mice rescued the induction of IL-17 and IL-22 by S. aureus and improved bacterial clearance. Finally, exogenous IL-1\u03b2 did not significantly rescue S. aureus host defense during coinfection in IL-17RA\u2212\/\u2212 mice or in mice in which IL-17 and IL-22 activity were blocked. These data reveal a novel mechanism by which Influenza A inhibits S. aureus\u2013induced IL-1\u03b2 production, resulting in attenuation of Type 17 immunity and increased susceptibility to bacterial infection.<\/jats:p>","DOI":"10.4049\/jimmunol.1301237","type":"journal-article","created":{"date-parts":[[2013,10,2]],"date-time":"2013-10-02T21:17:19Z","timestamp":1380748639000},"page":"5153-5159","source":"Crossref","is-referenced-by-count":127,"title":["Influenza A Exacerbates\n                    <i>Staphylococcus aureus<\/i>\n                    Pneumonia by Attenuating IL-1\u03b2 Production in Mice"],"prefix":"10.1093","volume":"191","author":[{"given":"Keven M","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"},{"name":"Department of Medicine, University of Pittsburgh Medical Center , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Mi","family":"Choi","sequence":"additional","affiliation":[{"name":"Richard K. Mellon Foundation Institute, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J","family":"McHugh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivanarayana","family":"Mandalapu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard I","family":"Enelow","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dartmouth Medical School , Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K","family":"Kolls","sequence":"additional","affiliation":[{"name":"Richard K. Mellon Foundation Institute, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Alcorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center , Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,11,15]]},"reference":[{"key":"2025032405575323200_r1","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1001\/archpediatrics.2010.295","article-title":"Influenza coinfection and outcomes in children with complicated pneumonia","volume":"165","author":"Williams","year":"2011","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"2025032405575323200_r2","first-page":"1476","article-title":"Comparison of community-acquired pneumonia due to methicillin-resistant and methicillin-susceptible Staphylococcus aureus producing the Panton-Valentine leukocidin","volume":"13","author":"Vardakas","year":"2009","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"2025032405575323200_r3","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1038\/nature06096","article-title":"Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome","volume":"448","author":"Minegishi","year":"2007","journal-title":"Nature"},{"key":"2025032405575323200_r4","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nature06764","article-title":"Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome","volume":"452","author":"Milner","year":"2008","journal-title":"Nature"},{"key":"2025032405575323200_r5","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbagen.2011.02.002","article-title":"T(H)17 cells in asthma and inflammation","volume":"1810","author":"Aujla","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"2025032405575323200_r6","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nri2295","article-title":"TH17 cells in development: an updated view of their molecular identity and genetic programming","volume":"8","author":"Dong","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025032405575323200_r7","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1084\/jem.20061308","article-title":"Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides","volume":"203","author":"Liang","year":"2006","journal-title":"J. Exp. Med."},{"key":"2025032405575323200_r8","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.immuni.2009.02.007","article-title":"Critical regulation of early Th17 cell differentiation by interleukin-1 signaling","volume":"30","author":"Chung","year":"2009","journal-title":"Immunity"},{"key":"2025032405575323200_r9","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/nature09447","article-title":"Generation of pathogenic T(H)17 cells in the absence of TGF-\u03b2 signalling","volume":"467","author":"Ghoreschi","year":"2010","journal-title":"Nature"},{"key":"2025032405575323200_r10","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.4049\/jimmunol.1200086","article-title":"Mouse CD11b+Gr-1+ myeloid cells can promote Th17 cell differentiation and experimental autoimmune encephalomyelitis","volume":"189","author":"Yi","year":"2012","journal-title":"J. Immunol."},{"key":"2025032405575323200_r11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.immuni.2008.03.001","article-title":"Th17 cell differentiation: the long and winding road","volume":"28","author":"McGeachy","year":"2008","journal-title":"Immunity"},{"key":"2025032405575323200_r12","doi-asserted-by":"crossref","first-page":"9358","DOI":"10.1074\/jbc.C600321200","article-title":"STAT3 regulates cytokine-mediated generation of inflammatory helper T cells","volume":"282","author":"Yang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2025032405575323200_r13","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":"Kudva","year":"2011","journal-title":"J. Immunol."},{"key":"2025032405575323200_r14","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":"Ichinohe","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032405575323200_r15","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1007\/s10875-010-9440-3","article-title":"Molecular mechanism of NLRP3 inflammasome activation","volume":"30","author":"Jin","year":"2010","journal-title":"J. Clin. Immunol."},{"key":"2025032405575323200_r16","doi-asserted-by":"crossref","first-page":"36560","DOI":"10.1074\/jbc.M607594200","article-title":"Critical role for Cryopyrin\/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA","volume":"281","author":"Kanneganti","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025032405575323200_r17","doi-asserted-by":"crossref","first-page":"6933","DOI":"10.4049\/jimmunol.179.10.6933","article-title":"Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo","volume":"179","author":"Miller","year":"2007","journal-title":"J. Immunol."},{"key":"2025032405575323200_r18","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1084\/jem.194.4.519","article-title":"Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense","volume":"194","author":"Ye","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032405575323200_r19","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/0008-8749(77)90170-8","article-title":"Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes","volume":"33","author":"Braciale","year":"1977","journal-title":"Cell. Immunol."},{"key":"2025032405575323200_r20","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1038\/sj.gt.3301335","article-title":"Immunogenicity of enhanced green fluorescent protein (EGFP) in BALB\/c mice: identification of an H2-Kd-restricted CTL epitope","volume":"7","author":"Gambotto","year":"2000","journal-title":"Gene Ther."},{"key":"2025032405575323200_r21","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1128\/jvi.71.3.1842-1849.1997","article-title":"Construction of adenovirus vectors through Cre-lox recombination","volume":"71","author":"Hardy","year":"1997","journal-title":"J. Virol."},{"key":"2025032405575323200_r22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/ni.1824","article-title":"Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production","volume":"11","author":"Poeck","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032405575323200_r23","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":"Martinon","year":"2002","journal-title":"Mol. Cell"},{"key":"2025032405575323200_r24","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.imbio.2008.11.007","article-title":"Mechanisms of interleukin-1beta release","volume":"214","author":"Eder","year":"2009","journal-title":"Immunobiology"},{"key":"2025032405575323200_r25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1165\/rcmb.2011-0267OC","article-title":"Rhinovirus-induced IL-1\u03b2 release from bronchial epithelial cells is independent of functional P2X7","volume":"47","author":"Shi","year":"2012","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2025032405575323200_r26","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.immuni.2009.08.001","article-title":"Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity","volume":"31","author":"Sutton","year":"2009","journal-title":"Immunity"},{"key":"2025032405575323200_r27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.imlet.2004.06.010","article-title":"Regulatory roles of IL-17 and IL-17F in G-CSF production by lung microvascular endothelial cells stimulated with IL-1beta and\/or TNF-alpha","volume":"95","author":"Numasaki","year":"2004","journal-title":"Immunol. Lett."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/10\/5153\/62506790\/1301237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/191\/10\/5153\/62506790\/1301237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T06:59:41Z","timestamp":1742885981000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/191\/10\/5153\/7966624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,11,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1301237","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,11]]},"published":{"date-parts":[[2013,11]]}}}