Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida.

Détails

ID Serval
serval:BIB_3CC7B50D4A9A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida.
Périodique
Nature Immunology
Auteur(s)
Meunier E., Wallet P., Dreier R.F., Costanzo S., Anton L., Rühl S., Dussurgey S., Dick M.S., Kistner A., Rigard M., Degrandi D., Pfeffer K., Yamamoto M., Henry T., Broz P.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
16
Numéro
5
Pages
476-484
Langue
anglais
Résumé
The AIM2 inflammasome detects double-stranded DNA in the cytosol and induces caspase-1-dependent pyroptosis as well as release of the inflammatory cytokines interleukin 1β (IL-1β) and IL-18. AIM2 is critical for host defense against DNA viruses and bacteria that replicate in the cytosol, such as Francisella tularensis subspecies novicida (F. novicida). The activation of AIM2 by F. novicida requires bacteriolysis, yet whether this process is accidental or is a host-driven immunological mechanism has remained unclear. By screening nearly 500 interferon-stimulated genes (ISGs) through the use of small interfering RNA (siRNA), we identified guanylate-binding proteins GBP2 and GBP5 as key activators of AIM2 during infection with F. novicida. We confirmed their prominent role in vitro and in a mouse model of tularemia. Mechanistically, these two GBPs targeted cytosolic F. novicida and promoted bacteriolysis. Thus, in addition to their role in host defense against vacuolar pathogens, GBPs also facilitate the presentation of ligands by directly attacking cytosolic bacteria.

Mots-clé
Animals, Bacteriolysis, Cells, Cultured, Cytosol/microbiology, DNA-Binding Proteins/genetics, DNA-Binding Proteins/metabolism, Disease Models, Animal, Francisella tularensis/physiology, GTP-Binding Proteins/genetics, GTP-Binding Proteins/metabolism, Humans, Inflammasomes/metabolism, Mice, Mice, Knockout, RNA, Small Interfering/genetics, Tularemia/immunology
Pubmed
Web of science
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 14:32
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