LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation.

Détails

ID Serval
serval:BIB_C2F39FFB50CB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
LPS targets host guanylate-binding proteins to the bacterial outer membrane for non-canonical inflammasome activation.
Périodique
The EMBO journal
Auteur(s)
Santos J.C., Dick M.S., Lagrange B., Degrandi D., Pfeffer K., Yamamoto M., Meunier E., Pelczar P., Henry T., Broz P.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
15/03/2018
Peer-reviewed
Oui
Volume
37
Numéro
6
Pages
1-19
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Pathogenic and commensal Gram-negative bacteria produce and release outer membrane vesicles (OMVs), which present several surface antigens and play an important role for bacterial pathogenesis. OMVs also modulate the host immune system, which makes them attractive as vaccine candidates. At the cellular level, OMVs are internalized by macrophages and deliver lipopolysaccharide (LPS) into the host cytosol, thus activating the caspase-11 non-canonical inflammasome. Here, we show that OMV-induced inflammasome activation requires TLR4-TRIF signaling, the production of type I interferons, and the action of guanylate-binding proteins (GBPs), both in macrophages and <i>in vivo</i> Mechanistically, we find that isoprenylated GBPs associate with the surface of OMVs or with transfected LPS, indicating that the key factor that determines GBP recruitment to the Gram-negative bacterial outer membranes is LPS itself. Our findings provide new insights into the mechanism by which GBPs target foreign surfaces and reveal a novel function for GBPs in controlling the intracellular detection of LPS derived from extracellular bacteria in the form of OMVs, thus extending their function as a hub between cell-autonomous immunity and innate immunity.
Mots-clé
Animals, Bacteria/immunology, Cell Membrane/immunology, GTP-Binding Proteins/genetics, GTP-Binding Proteins/immunology, Inflammasomes/immunology, Lipopolysaccharides/immunology, Mice, Inbred C57BL, Mice, Knockout, LPS, caspase‐11, guanylate‐binding proteins (GBPs), inflammasome, outer membrane vesicles
Pubmed
Web of science
Création de la notice
01/03/2018 20:20
Dernière modification de la notice
20/08/2019 16:38
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