In vivo IFN-γ secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes

Andreas Kupz, Roy Curtiss, Sammy Bedoui, Richard A. Strugnell

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Natural killer (NK) cells are a critical part of the innate immune defense against viral infections and for the control of tumors. Much less is known about how NK cells contribute to anti-bacterial immunity. NK cell-produced interferon gamma (IFN-γ) contributes to the control of early exponential replication of bacterial pathogens, however the regulation of these events remains poorly resolved. Using a mouse model of invasive Salmonellosis, here we report that the activation of the intracellular danger sensor NLRC4 by Salmonella -derived flagellin within CD11c+ cells regulates early IFN-γ secretion by NK cells through the provision of interleukin 18 (IL-18), independently of Toll-like receptor (TLR)-signaling. Although IL18-signalling deficient NK cells improved host protection during S. Typhimurium infection, this increased resistance was inferior to that provided by wild-type NK cells. These findings suggest that although NLRC4 inflammasome-driven secretion of IL18 serves as a potent activator of NK cell mediated IFN-c secretion, IL18-independent NK cell-mediated mechanisms of IFN-γ secretion contribute to in vivo control of Salmonella replication.

Original languageEnglish (US)
Article numbere97418
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 14 2014

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Inflammasomes
Interleukin-18
Salmonella
natural killer cells
Salmonella typhimurium
Salmonella Typhimurium
Natural Killer Cells
secretion
Flagellin
Toll-Like Receptors
Pathogens
Interferon-gamma
Tumors
Chemical activation
interleukin-18
flagellin
Salmonella Infections
Sensors
salmonellosis
Virus Diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

In vivo IFN-γ secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes. / Kupz, Andreas; Curtiss, Roy; Bedoui, Sammy; Strugnell, Richard A.

In: PLoS One, Vol. 9, No. 5, e97418, 14.05.2014.

Research output: Contribution to journalArticle

Kupz, Andreas ; Curtiss, Roy ; Bedoui, Sammy ; Strugnell, Richard A. / In vivo IFN-γ secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes. In: PLoS One. 2014 ; Vol. 9, No. 5.
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