{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T03:38:19Z","timestamp":1780544299635,"version":"3.54.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>A frequent sequela of influenza A virus (IAV) infection is secondary bacterial pneumonia. Therefore, it is clinically important to understand the genetic predisposition to IAV and bacterial coinfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>BALB\/c and C57BL\/6 (B6) mice were infected with high or low-pathogenic IAV and <jats:italic>Streptococcus pneumoniae<\/jats:italic> (<jats:italic>SPn<\/jats:italic>). The contribution of cellular and molecular immune factors to the resistance\/susceptibility of BALB\/c and B6 mice were dissected in nonlethal and lethal IAV\/<jats:italic>SPn<\/jats:italic> coinfection models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low-virulent IAV X31 (H3N2) rendered B6 mice extremely susceptible to SPn superinfection, while BALB\/c mice remained unaffected. X31 infection alone barely induces IFN-\u03b3response in two strains of mice; however, SPn superinfection significantly enhances IFN-\u03b3 production in the susceptible B6 mice. As a result, IFN-\u03b3 signaling inhibits neutrophil recruitment and bacterial clearance, leading to lethal X31\/<jats:italic>SPn<\/jats:italic> coinfection in B6 mice. Conversely, the diminished IFN-\u03b3 and competent neutrophil responses enable BALB\/c mice highly resistant to X31\/SPn coinfection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The results establish that type 1 immune predisposition plays a key role in lethal susceptibility of B6 mice to pneumococcal pneumonia after mild IAV infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1272920","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T13:05:17Z","timestamp":1694610317000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Immune predisposition drives susceptibility to pneumococcal pneumonia after mild influenza A virus infection in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Sunil","family":"Palani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md 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