NLRC4 inflammasomes in DC's regulate noncognate effector function by memory CD8+ T cells

Diavatopoulos, Dimitri

Dr. Dimitri Diavatopoulos (Laboratory of Pediatric Infectious Diseases) has participated in an immunological study of the University of Melbourne aiming at unraveling the mechanistic framework for the regulation of noncognate memory T cell responses during bacterial immunity. The striking results have recently been published in Nature Immunology.

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 CD8a+ DCs were particularly efficient at sensing bacterial flagellin through NLRC4 inflammasomes. Although this activation released interleukin 18 (IL-18) and IL-1b, only IL-18 was required for IFN-g production by memory CD8+ T cells. Conversely, only the release of IL-1b, 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.

Kupz A, Guarda G, Gebhardt T, Sander LE, Short KR, Diavatopoulos DA, Wijburg OL, Cao H, Waithman JC, Chen W, Fernandez-Ruiz D, Whitney PG, Heath WR, Curtiss R 3rd, Tschopp J, Strugnell RA, Bedoui S. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8(+) T cells. Nat Immunol. 2012 Jan 8.

Photo: Dimitri Diavatopoulos


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