| First Author | Haraguchi N | Year | 2016 |
| Journal | Eur J Immunol | Volume | 46 |
| Issue | 7 | Pages | 1691-703 |
| PubMed ID | 27151377 | Mgi Jnum | J:246407 |
| Mgi Id | MGI:5924089 | Doi | 10.1002/eji.201545987 |
| Citation | Haraguchi N, et al. (2016) Activation of murine invariant NKT cells promotes susceptibility to candidiasis by IL-10 induced modulation of phagocyte antifungal activity. Eur J Immunol 46(7):1691-703 |
| abstractText | 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 Jalpha18-deficient mice (Jalpha18(-/-) ), which lack iNKT cells. Jalpha18(-/-) 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 alpha-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-1beta and IL-18, and caspase-1 activity were also significantly elevated in Jalpha18(-/-) mice after infection with C. albicans. The adoptive transfer of iNKT cells or exogenous administration of IL-10 into Jalpha18(-/-) 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. |
