{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:46:16Z","timestamp":1789055176776,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"MCubed","award":["U068874"],"award-info":[{"award-number":["U068874"]}]},{"name":"MCubed","award":["U064088"],"award-info":[{"award-number":["U064088"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pseudomonas aeruginosa (PA) is a pathogenic bacterium that causes severe pneumonia in critically ill and immunocompromised patients. Peptidylarginine deiminase (PAD) 2, PAD4, and caspase-1 are important enzymes in mediating host response to infection. The goal of this study was to determine the interplay between PAD2, PAD4, and caspase-1 in PA pneumonia-induced sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pneumonia was produced in wild-type, Pad2\u2212\/\u2212, and Pad4\u2212\/\u2212 mice by intranasal inoculation of PA (2.5\u2005\u00d7\u2005106 colony-forming units per mouse), and survival (n\u2005=\u200515\/group) was monitored for 10 days. Bone marrow-derived macrophages (BMDMs) were isolated for in vitro studies. Samples were collected at specific timepoints for Western blot, bacterial load determination, and flow cytometry analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Caspase-1-dependent inflammation was diminished in PA-inoculated Pad2\u2212\/\u2212 mice, contributing to reduced macrophage death and enhanced bacterial clearance. In addition, Pad2\u2212\/\u2212 mice exhibited improved survival and attenuated acute lung injury after PA infection. In contrast, Pad4\u2212\/\u2212 mice did not display diminished caspase-1 activation, altered bacterial loads, or improved survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Peptidylarginine deiminase 2 plays an essential role in the pathogenesis of pulmonary sepsis by mediating caspase-1 activation. This goes against previous findings of PAD4 in sepsis. Our study suggests that PAD2 is a potential therapeutic target of PA pneumonia-induced sepsis.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiaa475","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T19:12:10Z","timestamp":1595617930000},"page":"1093-1102","source":"Crossref","is-referenced-by-count":25,"title":["Peptidylarginine Deiminases 2 Mediates Caspase-1-Associated Lethality in<i>Pseudomonas aeruginosa<\/i>Pneumonia-Induced Sepsis"],"prefix":"10.1093","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4478-0734","authenticated-orcid":false,"given":"Zhenyu","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Michigan Hospital, Ann Arbor, Michigan, USA"},{"name":"Department of Infectious Diseases, Xiangya 2nd Hospital, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzi","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of 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