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

Details

Serval ID
serval:BIB_3CC7B50D4A9A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Guanylate-binding proteins promote activation of the AIM2 inflammasome during infection with Francisella novicida.
Journal
Nature Immunology
Author(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
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
16
Number
5
Pages
476-484
Language
english
Abstract
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.

Keywords
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
Create date
25/10/2017 10:05
Last modification date
20/08/2019 13:32
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