Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function

Anna Sokolovska, Christine E. Becker, Wai Kee Eddie Ip, Vijay A.K. Rathinam, Matthew Brudner, Nicholas Paquette, Antoine Tanne, Sivapriya K. Vanaja, Kathryn J. Moore, Katherine A. Fitzgerald, Adam Lacy-Hulbert, Lynda M. Stuart

Research output: Contribution to journalArticle

108 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)543-553
Number of pages11
JournalNature Immunology
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

Inflammasomes
Caspase 1
Phagosomes
NADPH Oxidase
Antigen Presentation
Gram-Positive Bacteria
Adaptive Immunity
Phagocytosis
Innate Immunity
Organelles
Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

Sokolovska, A., Becker, C. E., Ip, W. K. E., Rathinam, V. A. K., Brudner, M., Paquette, N., ... Stuart, L. M. (2013). Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. Nature Immunology, 14(6), 543-553. https://doi.org/10.1038/ni.2595

Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. / Sokolovska, Anna; Becker, Christine E.; Ip, Wai Kee Eddie; Rathinam, Vijay A.K.; Brudner, Matthew; Paquette, Nicholas; Tanne, Antoine; Vanaja, Sivapriya K.; Moore, Kathryn J.; Fitzgerald, Katherine A.; Lacy-Hulbert, Adam; Stuart, Lynda M.

In: Nature Immunology, Vol. 14, No. 6, 01.06.2013, p. 543-553.

Research output: Contribution to journalArticle

Sokolovska, A, Becker, CE, Ip, WKE, Rathinam, VAK, Brudner, M, Paquette, N, Tanne, A, Vanaja, SK, Moore, KJ, Fitzgerald, KA, Lacy-Hulbert, A & Stuart, LM 2013, 'Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function', Nature Immunology, vol. 14, no. 6, pp. 543-553. https://doi.org/10.1038/ni.2595
Sokolovska, Anna ; Becker, Christine E. ; Ip, Wai Kee Eddie ; Rathinam, Vijay A.K. ; Brudner, Matthew ; Paquette, Nicholas ; Tanne, Antoine ; Vanaja, Sivapriya K. ; Moore, Kathryn J. ; Fitzgerald, Katherine A. ; Lacy-Hulbert, Adam ; Stuart, Lynda M. / Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function. In: Nature Immunology. 2013 ; Vol. 14, No. 6. pp. 543-553.
@article{c1a41d594487432fa48afe8c7ac818b0,
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.",
author = "Anna Sokolovska and Becker, {Christine E.} and Ip, {Wai Kee Eddie} and Rathinam, {Vijay A.K.} and Matthew Brudner and Nicholas Paquette and Antoine Tanne and Vanaja, {Sivapriya K.} and Moore, {Kathryn J.} and Fitzgerald, {Katherine A.} and Adam Lacy-Hulbert and Stuart, {Lynda M.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1038/ni.2595",
language = "English (US)",
volume = "14",
pages = "543--553",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function

AU - Sokolovska, Anna

AU - Becker, Christine E.

AU - Ip, Wai Kee Eddie

AU - Rathinam, Vijay A.K.

AU - Brudner, Matthew

AU - Paquette, Nicholas

AU - Tanne, Antoine

AU - Vanaja, Sivapriya K.

AU - Moore, Kathryn J.

AU - Fitzgerald, Katherine A.

AU - Lacy-Hulbert, Adam

AU - Stuart, Lynda M.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878245034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878245034&partnerID=8YFLogxK

U2 - 10.1038/ni.2595

DO - 10.1038/ni.2595

M3 - Article

C2 - 23644505

AN - SCOPUS:84878245034

VL - 14

SP - 543

EP - 553

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 6

ER -