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., and Bedoui, Sammy (2012) NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8⁺ T cells. Nature Immunology, 13 (2). pp. 162-169.

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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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