{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:31:49Z","timestamp":1791952309922,"version":"4.3.4"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Streptococcus pneumoniae<\/jats:named-content>\n            (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.\n          <\/jats:p>","DOI":"10.1128\/iai.01278-12","type":"journal-article","created":{"date-parts":[[2013,1,15]],"date-time":"2013-01-15T04:54:12Z","timestamp":1358225652000},"page":"645-652","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Influenza-Induced Inflammation Drives Pneumococcal Otitis Media"],"prefix":"10.1128","volume":"81","author":[{"given":"Kirsty R.","family":"Short","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick C.","family":"Reading","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"},{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pedersen","sequence":"additional","affiliation":[{"name":"TissuPath Laboratories, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Gilbertson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma R.","family":"Job","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Edenborough","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marrit N.","family":"Habets","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldert","family":"Zomer","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter W. M.","family":"Hermans","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri A.","family":"Diavatopoulos","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odilia L.","family":"Wijburg","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200107000-00018"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1871"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-67-3-419"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000108197.81270.35"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/430954"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1802.102025"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a113053"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2011.00720.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.09.001"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1086\/341462"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00789-06"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.01.023"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.36.1.289-296.1982"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4292-4301.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir618"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-146779"},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","unstructured":"ShortKRDiavatopoulosDAReadingPCBrownLERogersKLStrugnellRAWijburgOLC. 2011. Using bioluminescent imaging to investigate synergism between Streptococcus pneumoniae and influenza A virus in infant mice. J. Vis Exp. 2011:e2357. doi:10.3791\/2357.","DOI":"10.3791\/2357"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.16.9345"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-SobridoLGarc\u00eda-SastreA. 2010. Generation of recombinant influenza virus from plasmid DNA. J. Vis. Exp. 2011:e2057. doi:10.3791\/2057.","DOI":"10.3791\/2057"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.033175-0"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050170002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1530509100"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"DennisGJrShermanBTHosackDAYangJGaoWLaneHCLempickiRA. 2003. DAVID: database for annotation visualization and integrated discovery. Genome Biol. 4:P3. doi:10.1186\/gb-2003-4-5-p3.","DOI":"10.1186\/gb-2003-4-9-r60"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1177\/000348940211100606"},{"key":"e_1_3_3_26_2","first-page":"161","article-title":"Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion","volume":"13","author":"Smirnova MG","year":"2002","unstructured":"SmirnovaMGKiselevSLGnuchevNVBirchallJPPearsonJP. 2002. Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion. Eur. Cytokine Netw. 13:161\u2013172.","journal-title":"Eur. Cytokine Netw."},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.5.2562-2567.2006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/368163"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","unstructured":"McCullersJAKarlstr\u00f6m\u00c5IversonARLoefflerJMFischettiVA. 2007. Novel strategy to prevent otitis media caused by colonizing Streptococcus pneumoniae. PLoS Pathog. 3:e28. doi:10.1371\/journal.ppat.0030028.","DOI":"10.1371\/journal.ppat.0030028"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57762"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1086\/597042"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8204-8212.1997"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2004.06.012"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4289-4296.2003"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01278-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/IAI.01278-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T12:24:00Z","timestamp":1646483040000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/IAI.01278-12"}},"subtitle":[],"editor":[{"given":"L.","family":"Pirofski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2013,3]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1128\/IAI.01278-12"],"URL":"https:\/\/doi.org\/10.1128\/iai.01278-12","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3]]},"assertion":[{"value":"2012-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-11-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}