1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Background. Our interest in immunological effects produced by vitamin D-3 (1,25(OH)(2)D-3) and its therapeutic potential prompted us to examine the role of 1,25(OH)(2)D-3 on cytokine production by Candida albicans. Methods. Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH)(2)D-3, cytokine concentrations were measured in supernatant. Quantitative polymerase chain reaction (qPCR) was performed for T cell transcription factors, SOCS1 and 3. TLR2/4, Dectin-1, and mannose receptor expression was studied using flow cytometry and qPCR. An ex-vivo stimulation study was carried out in healthy volunteers to investigate the seasonality of immune response to C. albicans. Results. Upon in vitro C. albicans stimulation, 1,25(OH)(2)D-3 induced a dose-dependent, down-regulation of IL-6, TNF alpha, IL-17, and IFN gamma. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH)(2)D-3 augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH)(2)D-3 inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFN gamma levels were suppressed in summer when 25(OH)D-3 levels were elevated. Conclusion. Vitamin D-3 skews cytokine responses toward an antiinflammatory profile, mediated by suppression of TLR2, TLR4, Dectin-1, and MR transcription, leading to reduced surface expression. The biological relevance of these effects has been confirmed by the seasonality of cytokine responses.