In vivo IFN-γ secretion by NK cells in response to Salmonella typhimurium requires NLRC4 inflammasomes.
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.
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia; Max Planck Institute for Infection Biology, Berlin, Germany; Queensland Tropical Health Alliance Research Laboratory, James Cook University, Cairns, Queensland, Australia.
Andreas
A
Kupz
Center of Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, United States of America.
Roy
R
Curtiss
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
Sammy
S
Bedoui
Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia.
Richard A
RA
Strugnell
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000276:immunology*; D002135:Calcium-Binding Proteins / Q000276:immunology*; D005408:Flagellin / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D058847:Inflammasomes / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; D020382:Interleukin-18; C512299:Ipaf protein, mouse; D051193:Toll-Like Receptors; D005408:Flagellin; D007371:Interferon-gamma