Interleukin-17-mediated adaptive immunity to Candida albicans in oropharyngeal candidiasis.

摘要

Oropharyngeal candidiasis is an opportunistic infection of the oral cavity caused by Candida albicans, a fungal member of the human commensal flora that causes disease only under conditions of immunosuppression. In HIV+ individuals, the onset of disease is directly correlated to a decrease in CD4+ T cell counts (<200 cells/mm3), suggesting that CD4+ T cells are important mediators of anti-Candida immunity. Previous studies demonstrated that IL-17 receptor A (IL-17RA) signaling is absolutely required for immunity to OPC. IL-17 is produced by a CD4+ T helper cell subset, Th17, and by a variety of innate immune cell types. Although it has always been assumed that CD4+ T cells are the primary mediators of immunity to C. albicans, the relative contribution of Th17 cells in the context of other, innate, sources of IL-17 had never been studied until now. We demonstrate that protective, antigen-specific Th17 cells develop upon secondary infection with C. albicans and contribute to fungal clearance from the tongue. Surprisingly, in the absence of CD4+ T cells, compensatory sources of IL-17, such as CD8+ T cells and CD3+CD4-CD8-, protect susceptible hosts from OPC. Our findings have important implications for designing vaccines targeted to immune compromised populations where it is necessary to harness residual immunity.