{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:19:11Z","timestamp":1789935551705,"version":"4.0.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T00:00:00Z","timestamp":1517443200000},"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":[[2018,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Influenza and bacterial coinfection is a significant cause of hospitalization and death in humans during influenza epidemics and pandemics. However, the fundamental protective and pathogenic mechanisms involved in this complex virus\u2013host\u2013bacterium interaction remain incompletely understood. In this study, we have developed mild to lethal influenza and Streptococcus pneumoniae coinfection models for comparative analyses of disease pathogenesis. Specifically, wild-type and IL-1R type 1\u2013deficient (Il1r1\u2212\/\u2212) mice were infected with influenza virus and then superchallenged with noninvasive S. pneumoniae serotype 14 (Spn14) or S. pneumoniae serotype 19A (Spn19A). The coinfections were followed by comparative analyses of inflammatory responses and animal protection. We found that resident alveolar macrophages are efficient in the clearance of both pneumococcal serotypes in the absence of influenza infection; in contrast, they are essential for airway control of Spn14 infection but not Spn19A infection. In agreement, TNF-\u03b1 and neutrophils play a compensatory protective role in secondary bacterial infection associated with Spn19A; however, the essential requirement for alveolar macrophage\u2013mediated clearance significantly enhances the virulence of Spn14 during postinfluenza pneumococcal infection. Furthermore, we show that, although IL-1 signaling is not required for host defense against pneumococcal infection alone, it is essential for sustaining antibacterial immunity during postinfluenza pneumococcal infection, as evidenced by significantly aggravated bacterial burden and animal mortality in Il1r1\u2212\/\u2212 mice. Mechanistically, we show that through preventing alveolar macrophage depletion, inflammatory cytokine IL-1 signaling is critically involved in host resistance to influenza and pneumococcal coinfection.<\/jats:p>","DOI":"10.4049\/jimmunol.1700210","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T15:30:17Z","timestamp":1515425417000},"page":"1425-1433","source":"Crossref","is-referenced-by-count":40,"title":["IL-1 Signaling Prevents Alveolar Macrophage Depletion during Influenza and <i>Streptococcus pneumoniae<\/i> Coinfection"],"prefix":"10.1093","volume":"200","author":[{"given":"Shruti","family":"Bansal","sequence":"first","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE 68198-5900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya Kumar","family":"Yajjala","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE 68198-5900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-9582","authenticated-orcid":false,"given":"Christopher","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE 68198-5900"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-9584","authenticated-orcid":false,"given":"Keer","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE 68198-5900"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"2025030610015871200_r1","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4049\/jimmunol.1301152","article-title":"Immune dysfunction and bacterial coinfections following influenza","volume":"191","author":"Metzger","year":"2013","journal-title":"J. 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