Homeostatic defects in interleukin 18-deficient mice contribute to protection against the lethal effects of endotoxin

Daniel M. Andrews, Melvyn T Chow, Yuting Ma, Claire L Cotterell, Sally V Watt, Desiree A Anthony, Shizuo Akira, Yoichiro Iwakura, Joseph A. Trapani, Laurence Zitvogel, Mark J. Smyth

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12 Citations (Scopus)

Abstract

Toll-like receptor-4-lipopolysaccharide (LPS)-mediated inflammation is used to delineate signals involved in cross-talk between antigen-presenting cells (APCs) and lymphocytes such as natural killer (NK) cells. Following APC stimulation and cytokine release, NK cells produce interferon (IFN)-γ. High levels of LPS induce endotoxicosis, a systemic inflammatory disease in which IFN-γ causes significant morbidity and mortality. Several studies have highlighted the role of interleukin (IL)-18, IL-1Β, IL-17A and IFN-γ in the development of endotoxicosis, but whether these cytokines interact with each other is yet to be determined. Our data demonstrate that IL-18 and IL-17A have important roles in NK cell IFN-γ production during endotoxicosis. Importantly, we provide the first evidence that IL-18 also has a role in IL-17A production by T-cell receptor (TCR)-cells. Furthermore, we demonstrate that IL-18-deficient mice have a defect in γ T-cell homeostasis and IL-1Β production, both of which can contribute to the development of disease through induction of IL-17A. These results reveal novel requirements for IL-18 in innate immune cell homeostasis and activation, demonstrating that the role of IL-18 in innate immunity occurs at a level other than activation.

Original languageEnglish
Pages (from-to)739-746
Number of pages8
JournalImmunology and Cell Biology
Volume89
Issue number6
DOIs
Publication statusPublished - Aug 2011
Externally publishedYes

Keywords

  • γδ T cell
  • cross-talk
  • cytokines
  • innate immunity
  • natural killer

Cite this

Andrews, D. M., Chow, M. T., Ma, Y., Cotterell, C. L., Watt, S. V., Anthony, D. A., Akira, S., Iwakura, Y., Trapani, J. A., Zitvogel, L., & Smyth, M. J. (2011). Homeostatic defects in interleukin 18-deficient mice contribute to protection against the lethal effects of endotoxin. Immunology and Cell Biology, 89(6), 739-746. https://doi.org/10.1038/icb.2010.168