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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.
Animals, Apoptosis Regulatory Proteins/immunology, CD8-Positive T-Lymphocytes/immunology, Calcium-Binding Proteins/immunology, Dendritic Cells/immunology, Flagellin/immunology, Immunologic Memory, Inflammasomes/immunology, Interferon-gamma/immunology, Interleukin-18/immunology, Interleukin-1beta/immunology, Interleukin-1beta/secretion, Mice, Pseudomonas Infections/immunology, Pseudomonas aeruginosa/immunology, Salmonella Infections, Animal/immunology, Salmonella typhimurium/immunology, Signal Transduction/immunology, Spleen/immunology, Toll-Like Receptors/immunology, Yersinia pseudotuberculosis Infections/immunology
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