NLRC4 inflammasomes in dendritic cells regulate noncognate effector function by memory CD8+ T cells Academic Article uri icon

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.

authors

  • Kupz, Andreas
  • Guarda, Greta
  • Gebhardt, Thomas
  • Sander, Leif E
  • Short, Kirsty R
  • Diavatopoulos, Dimitri A
  • Wijburg, Odilia LC
  • 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

publication date

  • February 2012

has subject area