1,25-Dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: Impact of seasonal variation of immune responses

Abstract

Background. Our interest in immunological effects produced by vitamin D3 (1,25(OH)2D3) and its therapeutic potential prompted us to examine the role of 1,25(OH)2D3 on cytokine production by Candida albicans. Methods. Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH)2D3, 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)2D 3 induced a dose-dependent, down-regulation of IL-6, TNFα, IL-17, and IFNγ. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH)2D3 augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH) 2D3 inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFNγ levels were suppressed in summer when 25(OH)D3 levels were elevated. Conclusion. Vitamin D3 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. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.