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

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-? (IFN-?) 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?⁺ DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1?, only IL-18 was required for IFN-? production by memory CD8⁺ T cells. Conversely, only the release of IL-1?, 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. [ABSTRACT FROM AUTHOR]