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

Journal Publication ResearchOnline@JCU
Kupz, Andreas;Curtiss III, Roy;Bedoui, Sammy;Strugnell, Richard A.
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-γ secretion, IL18-independent NK cell-mediated mechanisms of IFN-γ secretion contribute to in vivo control of Salmonella replication.

Journal

PLoS ONE

Publication Name

N/A

Volume

9

ISBN/ISSN

1932-6203

Edition

N/A

Issue

5

Pages Count

5

Location

N/A

Publisher

Public Library of Science

Publisher Url

N/A

Publisher Location

N/A

Publish Date

N/A

Url

N/A

Date

N/A

EISSN

N/A

DOI

10.1371/journal.pone.0097418