{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:46:14Z","timestamp":1791830774376,"version":"4.3.4"},"posted":{"date-parts":[[2025,3,2]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T00:00:00Z","timestamp":1740873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R35GM124824"],"award-info":[{"award-number":["R35GM124824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01NS118014"],"award-info":[{"award-number":["R01NS118014"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["RF1NS134549"],"award-info":[{"award-number":["RF1NS134549"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The success of phagosome degradation relies on the ability of phagocytes to regulate the maturation of phagosomes. However, its underlying molecular mechanisms remain poorly understood. Here, we identify the proton-activated chloride (PAC) channel as a key negative regulator of phagosome maturation. PAC deletion enhanced phagosomal acidification and protease activities, leading to augmented bacterial killing in large peritoneal macrophages (LPMs) upon\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  infection in mice. Surprisingly, phagosome degradation also stimulated STING-IRF3-interferon responses and inflammasome activation in LPMs, both of which are enhanced upon PAC deletion. The increased inflammasome activation induced the release of cleaved gasdermin D, which localized to the surface of bacteria in the peritoneum and further contributed to their killing. Finally, enhanced bacterial clearance by PAC-deficient LPMs reduced proinflammatory immune cell infiltration and peritoneal inflammation, resulting in improved survival in mice. Our study thus provides new insights into the molecular mechanism of phagosome maturation and the dynamics of host defense response following phagosome-mediated bacterial degradation in peritoneal macrophages.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary<\/jats:title>\n                  <jats:p>The PAC channel mediates phagosome maturation during bacterial infection in macrophages. PAC deletion promotes phagosome-mediated STING-interferon signaling and inflammasome-mediated gasdermin D secretion during bacterial infection in peritoneal macrophages.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.27.640612","type":"posted-content","created":{"date-parts":[[2025,3,2]],"date-time":"2025-03-02T22:10:12Z","timestamp":1740953412000},"source":"Crossref","is-referenced-by-count":6,"title":["Phagosome-mediated anti-bacterial immunity is governed by the proton-activated chloride channel in peritoneal macrophages"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-4235","authenticated-orcid":false,"given":"Henry Yi","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachen","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathachit","family":"Limjunyawong","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Center of Research Excellence in Allergy and Immunology, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhi","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Koylass","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA"},{"name":"Solomon H. 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