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 language | English (US) |
|---|---|
| Pages (from-to) | 162-169 |
| Number of pages | 8 |
| Journal | Nature Immunology |
| Volume | 13 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2012 |
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ASJC Scopus subject areas
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8 + T cells
AU - Kupz, Andreas
AU - Guarda, Greta
AU - Gebhardt, Thomas
AU - Sander, Leif E.
AU - Short, Kirsty R.
AU - Diavatopoulos, Dimitri A.
AU - Wijburg, Odilia L C
AU - Cao, Hanwei
AU - Waithman, Jason C.
AU - Chen, Weisan
AU - Fernandez-Ruiz, Daniel
AU - Whitney, Paul G.
AU - Heath, William R.
AU - Curtiss, Roy
AU - Tschopp, Jürg
AU - Strugnell, Richard A.
AU - Bedoui, Sammy
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
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U2 - 10.1038/ni.2195
DO - 10.1038/ni.2195
M3 - Article
VL - 13
SP - 162
EP - 169
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 2
ER -