IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection.

Détails

Ressource 1Télécharger: journal.ppat.1006630.pdf (12327.61 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_C56F249390E0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection.
Périodique
PLoS Pathogens
Auteur(s)
Wallet P., Benaoudia S., Mosnier A., Lagrange B., Martin A., Lindgren H., Golovliov I., Michal F., Basso P., Djebali S., Provost A., Allatif O., Meunier E., Broz P., Yamamoto M., Py B.F., Faudry E., Sjöstedt A., Henry T.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
13
Numéro
10
Pages
e1006630
Langue
anglais
Résumé
Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes complexes and apoptotic caspases. IFN-γ induces a quantitative switch in GBPs levels and redirects pyroptotic and apoptotic pathways under the control of GBPs. Furthermore, upon IFN-γ priming, F. novicida-infected macrophages restrict cytosolic bacterial replication in a GBP-dependent and inflammasome-independent manner. Finally, in a mouse model of tularemia, we demonstrate that the inflammasome and the GBPs are two key immune pathways functioning largely independently to control F. novicida infection. Altogether, our results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners.

Mots-clé
Animals, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Fluorescent Antibody Technique, Francisella, Francisella tularensis/immunology, GTP-Binding Proteins/immunology, Gene Knockdown Techniques, Gram-Negative Bacterial Infections/immunology, Immunoblotting, Inflammasomes/immunology, Interferon-gamma/immunology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Tularemia/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 16:41
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