title: Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL-10 induced modulation of phagocyte antifungal activity.
abstract: 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 Jα18-deficient mice (Jα18(-/-) ), which lack iNKT cells. Jα18(-/-) 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 α-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-1β and IL-18, and caspase-1 activity were also significantly elevated in Jα18(-/-) mice after infection with C. albicans. The adoptive transfer of iNKT cells or exogenous administration of IL-10 into Jα18(-/-) 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.
authors.affiliation: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Haraguchi
authors.affiliation: Department of Respiratory Medicine, Kasumigaura Medical Center, Tsuchiura, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kikuchi
authors.affiliation: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Matsuyama
authors.affiliation: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Sakurai
authors.affiliation: Department of Immunology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.affiliation: Department of Immunology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Laboratory of Immune Regulation, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Department of Respiratory Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishii
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002175:Candida / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009026:Mortality; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism*; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10
keywords: Candidiasis; IL-10; Inflammasome; Macrophages; iNKT cells