title: Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function.
abstract: Phagocytosis 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 many functions of these organelles that allow phagosomes to participate in processes that are 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.
authors: Developmental Immunology and Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. asokolovska@partners.org
authors: Anna
authors: A
authors: Sokolovska
authors: Christine E
authors: CE
authors: Becker
authors: W K Eddie
authors: WK
authors: Ip
authors: Vijay A K
authors: VA
authors: Rathinam
authors: Matthew
authors: M
authors: Brudner
authors: Nicholas
authors: N
authors: Paquette
authors: Antoine
authors: A
authors: Tanne
authors: Sivapriya K
authors: SK
authors: Vanaja
authors: Kathryn J
authors: KJ
authors: Moore
authors: Katherine A
authors: KA
authors: Fitzgerald
authors: Adam
authors: A
authors: Lacy-Hulbert
authors: Lynda M
authors: LM
authors: Stuart
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D020170:Caspase 1 / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000276:immunology* / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D008562:Membrane Glycoproteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D020170:Caspase 1
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