{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:08:37Z","timestamp":1791209317865,"version":"4.1.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,7,7]],"date-time":"2021-07-07T00:00:00Z","timestamp":1625616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M662206"],"award-info":[{"award-number":["2019M662206"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anhui Provincial Postdoctoral Science Research Project","award":["2019B377"],"award-info":[{"award-number":["2019B377"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Streptococcus pneumoniae co-infection post-influenza is a major cause of mortality characterized by uncontrolled bacteria burden and excessive immune response during influenza pandemics. Interleukin (IL)-4 is a canonical type II immune cytokine known for its wide range of biological activities on different cell types. It displays protective roles in numerous infectious diseases and immune-related diseases, but its role in influenza and S. pneumoniae (influenza\/S. pneumoniae) co-infected pneumonia has not been reported. In our study, we used C57BL\/6 wild-type (WT) and IL-4-deficient (IL-4\u2212\/\u2212) mice to establish co-infection model with S. pneumoniae after influenza virus infection. Co-infected IL-4\u2212\/\u2212 mice showed increased mortality and weight loss compared with WT mice. IL-4 deficiency led to increased bacterial loads in lungs without altering influenza virus replication, suggesting a role of IL-4 in decreasing post-influenza susceptibility to S. pneumoniae co-infection. Loss of IL-4 also resulted in aggravated lung damage together with massive proinflammatory cytokine production and immune cell infiltration during co-infection. Administration of recombinant IL-4 rescued the survival and weight loss of IL-4\u2212\/\u2212 mice in lethal co-infection. Additionally, IL-4 deficiency led to more immune cell death in co-infection. Gasdermin D (GSDMD) during co-infection was induced in IL-4\u2212\/\u2212 mice that subsequently activated cell pyroptosis. Treatment of recombinant IL-4 or inhibition of GSDMD activity by disulfiram decreased immune cell death and bacterial loads in lungs of IL-4\u2212\/\u2212 co-infected mice. These results suggest that IL-4 decreases post-influenza susceptibility to S. pneumoniae co-infection via suppressing GSDMD-induced pyroptosis. Collectively, this study demonstrates the protective role of IL-4 in influenza\/S. pneumoniae co-infected pneumonia.<\/jats:p>","DOI":"10.1111\/cei.13628","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T16:58:20Z","timestamp":1622566700000},"page":"379-390","source":"Crossref","is-referenced-by-count":12,"title":["Interleukin-4 protects mice against lethal influenza and <i>Streptococcus pneumoniae<\/i> co-infected pneumonia"],"prefix":"10.1093","volume":"205","author":[{"given":"Yang","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine, Chongqing Medical University, Chongqing, China"},{"name":"Division of Life 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