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

Andreas Kupz, Greta Guarda, Thomas Gebhardt, Leif E. Sander, Kirsty R. Short, Dimitri A. Diavatopoulos, Odilia L C Wijburg, Hanwei Cao, Jason C. Waithman, Weisan Chen, Daniel Fernandez-Ruiz, Paul G. Whitney, William R. Heath, Roy Curtiss, Jürg Tschopp, Richard A. Strugnell, Sammy Bedoui

Research output: Contribution to journalArticle

98 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalNature Immunology
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2012

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kupz, A., Guarda, G., Gebhardt, T., Sander, L. E., Short, K. R., Diavatopoulos, D. A., Wijburg, O. L. C., Cao, H., Waithman, J. C., Chen, W., Fernandez-Ruiz, D., Whitney, P. G., Heath, W. R., Curtiss, R., Tschopp, J., Strugnell, R. A., & Bedoui, S. (2012). NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells. Nature Immunology, 13(2), 162-169. https://doi.org/10.1038/ni.2195