NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8⁺ T cells

Kupz, Andreas;Guarda, Greta;Gebhardt, Thomas;Sander, Leif E.;Short, Kirsty R.;Diavatopoulos, Dimitri A.;Wijburg, Odilia L.C.;Cao, Hanwei;Waithman, Jason C.;Chen, Weisan;Fernandez-Ruiz, Daniel;Whitney, Paul G.;Heath, William R.;Curtis, Roy;Tschopp, Jürg;Strugnell, Richard A.;Bedoui, Sammy

Andreas Kupz

Abstract

Memory T cells exert antigen-independent effector functions, but how these responses are regulated is unclear. We discovered an in vivo link between flagellin-induced NLRC4 inflammasome activation in splenic dendritic cells (DCs) and host protective interferon- g (IFN- g ) secretion by noncognate memory CD8 + T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8 a + DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1 b , only IL-18 was required for IFN- g production by memory CD8 + T cells. Conversely, only the release of IL-1 b , but not IL-18, depended on priming signals mediated by Toll-like receptors. These findings provide a comprehensive mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity.

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Nature Immunology

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1529-2916

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Nature Publishing Group

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DOI

10.1038/ni.2195