Epithelium-Intrinsic NAIP/NLRC4 Inflammasome Drives Infected Enterocyte Expulsion to Restrict Salmonella Replication in the Intestinal Mucosa.

Détails

ID Serval
serval:BIB_109988F1DCD4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Epithelium-Intrinsic NAIP/NLRC4 Inflammasome Drives Infected Enterocyte Expulsion to Restrict Salmonella Replication in the Intestinal Mucosa.
Périodique
Cell Host and Microbe
Auteur(s)
Sellin M.E., Müller A.A., Felmy B., Dolowschiak T., Diard M., Tardivel A., Maslowski K.M., Hardt W.D.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Statut éditorial
Publié
Date de publication
2014
Volume
16
Numéro
2
Pages
237-248
Langue
anglais
Résumé
The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/09/2014 8:31
Dernière modification de la notice
20/08/2019 12:37
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