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., 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.

Item ID: 30942
Item Type: Article (Research - C1)
ISSN: 1529-2916
Funders: National Health and Medical Research Council (NHMRC) of Australia, Louis-Jeantet Foundation, Gates Foundation
Date Deposited: 25 Jun 2014 04:12
FoR Codes: 06 BIOLOGICAL SCIENCES > 0605 Microbiology > 060502 Infectious Agents @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110707 Innate Immunity @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 30%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 45%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 35%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 20%
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