Phagosome-mediated anti-bacterial immunity is governed by the proton-activated chloride channel in peritoneal macrophages.

ABSTRACT: 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 Escherichia coli 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 pe

SUBMITTER: Cheng HY 

PROVIDER: S-EPMC11888413 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature