1. Homeostatic defects in interleukin 18-deficient mice contribute to protection against the lethal effects of endotoxin.
- Author
-
Andrews, Daniel M., Chow, Melvyn T., Yuting Ma, Cotterell, Claire L., Watt, Sally V., Anthony, Desiree A., Akira, Shizuo, Iwakura, Yoichiro, Trapani, Joseph A., Zitvogel, Laurence, and Smyth, Mark J.
- Subjects
- *
NATURAL immunity , *KILLER cells , *T cells , *CYTOKINES , *ENDOTOXINS , *LYMPHOCYTES , *INTERLEUKINS , *CELL receptors - 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)-δ cells. Furthermore, we demonstrate that IL-18-deficient mice have a defect in γδ 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. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF