Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function
Autor: | Sivapriya Kailasan Vanaja, Antoine Tanne, Adam Lacy-Hulbert, Anna Sokolovska, Nicholas Paquette, W. K. Eddie Ip, Vijay A. K. Rathinam, Katherine A. Fitzgerald, Christine Becker, Lynda M. Stuart, Matthew Brudner, Kathryn J. Moore |
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Rok vydání: | 2013 |
Předmět: |
Staphylococcus aureus
Mice 129 Strain Inflammasomes Phagosome acidification Phagocytosis Immunoblotting Immunology Caspase 1 Mice Transgenic Article Mice 03 medical and health sciences 0302 clinical medicine Phagosomes NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Humans Immunology and Allergy Cells Cultured 030304 developmental biology Phagosome Mice Knockout 0303 health sciences Membrane Glycoproteins Microscopy Confocal Innate immune system NADPH oxidase biology Macrophages NADPH Oxidases Inflammasome Hydrogen-Ion Concentration Flow Cytometry Acquired immune system Cell biology Enzyme Activation Mice Inbred C57BL Microscopy Electron HEK293 Cells 030220 oncology & carcinogenesis Host-Pathogen Interactions NADPH Oxidase 2 biology.protein Carrier Proteins Reactive Oxygen Species medicine.drug |
Zdroj: | Nature immunology |
ISSN: | 1529-2916 1529-2908 |
Popis: | 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. |
Databáze: | OpenAIRE |
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