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
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