Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.

Détails

ID Serval
serval:BIB_8C5CB24445D8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant strains is attributed to increased intracellular bacteriolysis.
Périodique
Cellular Microbiology
Auteur(s)
Peng K., Broz P., Jones J., Joubert L.M., Monack D.
ISSN
1462-5822 (Electronic)
ISSN-L
1462-5814
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
13
Numéro
10
Pages
1586-1600
Langue
anglais
Résumé
Intracellular bacterial pathogens Francisella novicida and the Live Vaccine Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome, which leads to the activation of caspase-1 and the processing and secretion of active IL-1β, IL-18 and pyroptosis. Previous studies have reported that F. novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce elevated inflammasome activation and hypercytotoxicity in host cells, leading to the proposal that F. novicida and LVS may have proteins that actively modulate inflammasome activation. However, there has been no direct evidence of such inflammasome evasion mechanisms. Here, we demonstrate for the first time that the above mutants, along with a wide range of F. novicida hypercytotoxic mutants that are deficient for membrane-associated proteins (ΔFTT0584, ΔmviN, ΔripA, ΔfopA and ΔFTN1217) or deficient for genes involved in O-antigen or LPS biosynthesis (ΔwbtA and ΔlpxH) lyse more intracellularly, thus activating increased levels of AIM2-dependent pyroptosis and other innate immune signalling pathways. This suggests that an inflammasome-specific evasion mechanism may not be present in F. novicida and LVS. Furthermore, future studies may need to consider increased bacterial lysis as a possible cause of elevated stimulation of multiple innate immune pathways when the protein composition or surface carbohydrates of the bacterial membrane is altered.

Mots-clé
Bacteriolysis, Caspase 1/metabolism, Cell Death, DNA-Binding Proteins, Francisella/immunology, Francisella/pathogenicity, Inflammasomes/metabolism, Macrophages/immunology, Macrophages/microbiology, Nuclear Proteins/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 15:50
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