Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function
Eddie Ip, WK
Rathinam, Vijay A.K.
Vanaja, Sivapriya K.
Moore, Kathryn J.
Fitzgerald, Katherine A.
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CitationSokolovska, A., C. E. Becker, W. Eddie Ip, V. A. Rathinam, M. Brudner, N. Paquette, A. Tanne, et al. 2013. “Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function.” Nature immunology 14 (6): 543-553. doi:10.1038/ni.2595. http://dx.doi.org/10.1038/ni.2595.
AbstractPhagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates a number of functions of these organelles that allow them to participate in processes essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3-inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3-inflammasome and caspase-1 in host defense.
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