Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.

Détails

ID Serval
serval:BIB_DFECC050B398
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Caspase-1 autoproteolysis is differentially required for NLRP1b and NLRP3 inflammasome function.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Guey B., Bodnar M., Manié S.N., Tardivel A., Petrilli V.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2014
Volume
111
Numéro
48
Pages
17254-17259
Langue
anglais
Résumé
Inflammasomes are caspase-1-activating multiprotein complexes. The mouse nucleotide-binding domain and leucine rich repeat pyrin containing 1b (NLRP1b) inflammasome was identified as the sensor of Bacillus anthracis lethal toxin (LT) in mouse macrophages from sensitive strains such as BALB/c. Upon exposure to LT, the NLRP1b inflammasome activates caspase-1 to produce mature IL-1β and induce pyroptosis. Both processes are believed to depend on autoproteolysed caspase-1. In contrast to human NLRP1, mouse NLRP1b lacks an N-terminal pyrin domain (PYD), indicating that the assembly of the NLRP1b inflammasome does not require the adaptor apoptosis-associated speck-like protein containing a CARD (ASC). LT-induced NLRP1b inflammasome activation was shown to be impaired upon inhibition of potassium efflux, which is known to play a major role in NLRP3 inflammasome formation and ASC dimerization. We investigated whether NLRP3 and/or ASC were required for caspase-1 activation upon LT stimulation in the BALB/c background. The NLRP1b inflammasome activation was assessed in both macrophages and dendritic cells lacking either ASC or NLRP3. Upon LT treatment, the absence of NLRP3 did not alter the NLRP1b inflammasome activity. Surprisingly, the absence of ASC resulted in IL-1β cleavage and pyroptosis, despite the absence of caspase-1 autoprocessing activity. By reconstituting caspase-1/caspase-11(-/-) cells with a noncleavable or catalytically inactive mutant version of caspase-1, we directly demonstrated that noncleavable caspase-1 is fully active in response to the NLRP1b activator LT, whereas it is nonfunctional in response to the NLRP3 activator nigericin. Taken together, these results establish variable requirements for caspase-1 cleavage depending on the pathogen and the responding NLR.
Mots-clé
interleukin-1beta, pyroptosis, lethal toxin, macrophage, dendritic cell
Pubmed
Web of science
Création de la notice
02/01/2015 9:29
Dernière modification de la notice
20/08/2019 16:04
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