Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing.

Détails

ID Serval
serval:BIB_A07BA81A5FA5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Differential requirement for Caspase-1 autoproteolysis in pathogen-induced cell death and cytokine processing.
Périodique
Cell Host & Microbe
Auteur(s)
Broz P., von Moltke J., Jones J.W., Vance R.E., Monack D.M.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
8
Numéro
6
Pages
471-483
Langue
anglais
Résumé
Activation of the cysteine protease Caspase-1 is a key event in the innate immune response to infections. Synthesized as a proprotein, Caspase-1 undergoes autoproteolysis within multiprotein complexes called inflammasomes. Activated Caspase-1 is required for proteolytic processing and for release of the cytokines interleukin-1β and interleukin-18, and it can also cause rapid macrophage cell death. We show that macrophage cell death and cytokine maturation in response to infection with diverse bacterial pathogens can be separated genetically and that two distinct inflammasome complexes mediate these events. Inflammasomes containing the signaling adaptor Asc form a single large "focus" in which Caspase-1 undergoes autoproteolysis and processes IL-1β/IL-18. In contrast, Asc-independent inflammasomes activate Caspase-1 without autoproteolysis and do not form any large structures in the cytosol. Caspase-1 mutants unable to undergo autoproteolysis promoted rapid cell death, but processed IL-1β/18 inefficiently. Our results suggest the formation of spatially and functionally distinct inflammasomes complexes in response to bacterial pathogens.

Mots-clé
Animals, Apoptosis Regulatory Proteins/physiology, Bacterial Infections/metabolism, Bacterial Infections/pathology, CARD Signaling Adaptor Proteins/physiology, Calcium-Binding Proteins/physiology, Caspase 1/genetics, Caspase 1/physiology, Cell Death, Cell Line, Cytokines/physiology, Cytoskeletal Proteins/physiology, DNA-Binding Proteins, Francisella/physiology, Inflammasomes/physiology, Legionella pneumophila/physiology, Macrophages/metabolism, Macrophages/microbiology, Macrophages/pathology, Mice, Mice, Inbred C57BL, Nuclear Proteins/metabolism, Protein Structure, Tertiary, Pseudomonas aeruginosa/physiology, Salmonella typhimurium/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 16:06
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