Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Article Dans Une Revue Mucosal Immunology Année : 2012

Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges

Résumé

Bacterial flagellin is a dominant innate immune activator of the intestine. Therefore, we examined the role of the intracellular flagellin receptor, NLRC4, in protecting the gut and/or driving inflammation. In accordance with NLRC4 acting through transcription-independent pathways, loss of NLRC4 did not reduce the rapid robust changes in intestinal gene expression induced by flagellin administration. Loss of NLRC4 did not alter basal intestinal homeostasis nor predispose mice to development of colitis upon administration of an anti-interleukin (IL)-10R monoclonal antibody. However, epithelial injury induced by dextran sulfate sodium in mice lacking NLRC4 resulted in a more severe disease, indicating a role for NLRC4 in protecting the gut. Moreover, loss of NLRC4 resulted in increased mortality in response to flagellate, but not aflagellate Salmonella infection. Thus, despite not being involved in rapid intestinal gene remodeling upon detection of flagellin, NLRC4-mediated inflammasome activation results in production of IL-1 beta and IL-18, two cytokines that protect mice from mucosal and systemic challenges.

Dates et versions

hal-02648191 , version 1 (29-05-2020)

Identifiants

Citer

F. A. Carvalho, I. Nalbantoglu, J. D. Aitken, R. Uchiyama, Y. Su, et al.. Cytosolic flagellin receptor NLRC4 protects mice against mucosal and systemic challenges. Mucosal Immunology, 2012, 5 (3), pp.288 - 298. ⟨10.1038/mi.2012.8⟩. ⟨hal-02648191⟩

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