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

Kupz, Andreas, Curtiss III, Roy, Bedoui, Sammy, and Strugnell, Richard A. (2014) In vivo IFN-γ secretion by NK cells in response to Salmonella Typhimurium requires NLRC4 inflammasomes. PLoS ONE, 9 (5). e97418. pp. 1-5.

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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.

Item ID: 37300
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

© 2014 Kupz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: National Health and Medical Research Council of Australia (NHMRC), Bill and Melinda Gates Foundation (BMGF)
Projects and Grants: NHMRC Program Grant Fighting Infection, exploiting host-pathogen interactions APP606788, NHMRC Career Development Award APP628464, NHMRC CJ Martin Biomedical Early Career Fellowship APP1052764, IH R01AI60557, Bill and Melinda Gates Foundation Grant no. 37863
Date Deposited: 15 Feb 2015 23:27
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 20%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110307 Gastroenterology and Hepatology @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 45%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 35%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 20%
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