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-γ (IFN-γ) secretion by noncognate memory CD8+ T cells, which could be activated by Salmonella enterica serovar Typhimurium, Yersinia pseudotuberculosis and Pseudomonas aeruginosa. We show that CD8α+ DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1β, only IL-18 was required for IFN-γ production by memory CD8+ T cells. Conversely, only the release of IL-1β, 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.

DOI: 10.1038/ni.2195

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@article{Kupz2012NLRC4II, title={NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8+ T cells}, author={Andreas Kupz and Greta Guarda and Thomas Gebhardt and Leif Erik Sander and Kirsty Renfree Short and Dimitri A. Diavatopoulos and Odilia L. C. Wijburg and Hanwei Cao and Jason C Waithman and Weisan Chen and Daniel Fernandez-Ruiz and Paul G. Whitney and William R Heath and Roy Curtiss and Juerg F. Tschopp and Richard A Strugnell and Sammy Bedoui}, journal={Nature Immunology}, year={2012}, volume={13}, pages={162-169} }