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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