Candida albicans Stimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by V delta 1 T Cells

• Published in: The Journal of immunology (1950) Vol. 194; no. 12; pp. 5953 - 5960
• Main Authors: Maher, Christina O, Dunne, Katie, Comerford, Ross, O'Dea, Siobhan, Loy, Aisling, Woo, James, Rogers, Thomas R, Mulcahy, Fiona, Dunne, Padraic J, Doherty, Derek G
• Format: Journal Article
• Language: English
• Published: 15.06.2015
• Subjects: Candida albicans; Human immunodeficiency virus
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.1403066

gamma delta T cells expressing the V delta 1 TCR are expanded in patients with HIV infection. We show in this article that circulating V delta 1 T cell numbers are particularly high in patients with HIV and candidiasis, and that these cells expand and produce IL-17 in response to Candida albicans in vitro. Although C. albicans could directly stimulate IL-17 production by a subset of V delta 1 T cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans-responsive V delta 1 T cells to generate sufficient numbers of cells to release IL-17 at levels detectable by ELISA. C. albicans induced the release of IL-1 beta , IL-6, and IL-23 by DCs, but addition of these cytokines or supernatants of C. albicans-treated DCs to V delta 1 T cells was not sufficient to induce proliferation. We found that direct contact with DCs was required for V delta 1 T cell proliferation, whereas IL-23R-blocking studies showed that IL-23 was required for optimal C. albicans-induced IL-17 production. Because IL-17 affords protection against both HIV and C. albicans, and because V delta 1 T cells are not depleted by HIV, these cells are likely to be an important source of IL-17 in HIV-infected patients with candidiasis, in whom CD4+ Th17 responses are impaired. These data show that C. albicans stimulates proliferation and IL-17 production by V delta 1 T cells by a mechanism that involves IL-23 release by DCs.