{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:00:56Z","timestamp":1780318856377,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013167","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000}}],"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370013"],"award-info":[{"award-number":["82370013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Bacterial lung infections cause severe host responses. Here, we showed that global deficiency of caspase-1 can protect against lethal pulmonary <jats:italic>Escherichia coli<\/jats:italic> infection by reducing the necroptosis of infiltrated neutrophils, which are key players in immune responses in the lung. Mechanistically, neutrophil necroptosis was not directly triggered in a cell-intrinsic manner by invading bacteria but was triggered by bacteria-stimulated pyroptotic epithelial cell supernatants <jats:italic>in vitro<\/jats:italic>. In validation experiments, chimeric mice with nonhematopoietic caspase-1 or GSDMD knockout were protected from lung <jats:italic>E. coli<\/jats:italic> infection and exhibited decreased neutrophil death. Nonhematopoietic pyroptosis facilitates the release of dsRNAs and contributes to neutrophil ZBP1-related necroptosis. Moreover, blocking dsRNA or depleting ZBP1 ameliorated the pathophysiological process of pulmonary <jats:italic>E. coli<\/jats:italic> infection. Overall, our results demonstrate a paradigm of communication between necroptosis and pyroptosis in different cell types in cooperation with microbes and hosts and suggest that therapeutic targeting of the pyroptosis or necroptosis pathway may prevent pulmonary bacterial infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013167","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T19:33:52Z","timestamp":1747164832000},"page":"e1013167","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Caspase-1-licensed pyroptosis drives dsRNA-mediated necroptosis and dampens host defense against bacterial 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