Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL-10 induced modulation of phagocyte antifungal activity

作者：Haraguchi Norihiro; Kikuchi Norihiro; Morishima Yuko; Matsuyama Masashi; Sakurai Hirofumi; Shibuya Akira; Shibuya Kazuko; Taniguchi Masaru; Ishii Yukio^*

来源：European Journal of Immunology, 2016, 46(7): 1691-1703.

DOI：10.1002/eji.201545987

• Candidiasis
• IL-10
• Inflammasome
• iNKT cells
• Macrophages

Invariant NKT (iNKT) cells play an important role in a variety of antimicrobial immune responses due to their ability to produce high levels of immune-modulating cytokines. Here, we investigated the role of iNKT cells in host defense against candidiasis using J alpha 18-deficient mice (J alpha 18(-/-)), which lack iNKT cells. J alpha 18(-/-) mice were more resistant to the development of lethal candidiasis than wild-type (WT) mice. In contrast, treatment of WT mice with the iNKT cell activating ligand a-galactosylceramide markedly enhanced their mortality after infection with Candida albicans. Serum IL-10 levels were significantly elevated in WT mice in response to infection with C. albicans. Futhermore, IL-10 production increased after in vitro coculture of peritoneal macrophages with iNKT cells and C. albicans. The numbers of peritoneal macrophages, the production of IL-1 beta and IL-18, and caspase-1 activity were also significantly elevated in J alpha 18(-/-) mice after infection with C. albicans. The adoptive transfer of iNKT cells or exogenous administration of IL-10 into J alpha 18(-/-) reversed susceptibility to candidiasis to the level of WT mice. These results suggest that activation of iNKT cells increases the initial severity of C. albicans infection, most likely mediated by IL-10 induced modulation of macrophage antifungal activity.

• 出版日期2016-7
• 单位RIKEN