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

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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-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 2012

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Inflammasomes
Dendritic Cells
Interleukin-18
T-Lymphocytes
Flagellin
Interleukin-1
Interferons
Yersinia pseudotuberculosis
Salmonella enterica
Toll-Like Receptors
Pseudomonas aeruginosa
Immunity
Antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Kupz, A., Guarda, G., Gebhardt, T., Sander, L. E., Short, K. R., Diavatopoulos, D. 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

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.; Curtiss, Roy; Tschopp, Jürg; Strugnell, Richard A.; Bedoui, Sammy.

In: Nature Immunology, Vol. 13, No. 2, 02.2012, p. 162-169.

Research output: Contribution to journalArticle

Kupz, A, Guarda, G, Gebhardt, T, Sander, LE, Short, KR, Diavatopoulos, DA, Wijburg, OLC, Cao, H, Waithman, JC, Chen, W, Fernandez-Ruiz, D, Whitney, PG, Heath, WR, Curtiss, R, Tschopp, J, Strugnell, RA & Bedoui, S 2012, 'NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells', Nature Immunology, vol. 13, no. 2, pp. 162-169. https://doi.org/10.1038/ni.2195
Kupz A, Guarda G, Gebhardt T, Sander LE, Short KR, Diavatopoulos DA et al. NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells. Nature Immunology. 2012 Feb;13(2):162-169. https://doi.org/10.1038/ni.2195
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. ; Curtiss, Roy ; Tschopp, Jürg ; Strugnell, Richard A. ; Bedoui, Sammy. / NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells. In: Nature Immunology. 2012 ; Vol. 13, No. 2. pp. 162-169.
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