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1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses.
Khoo, Ai-Leng; Chai, Louis Y A; Koenen, Hans J P M; Kullberg, Bart-Jan; Joosten, Irma; van der Ven, André J A M; Netea, Mihai G.
Afiliação
  • Khoo AL; Department of Laboratory Medicine, Radboud University Nijmegen Medical Center; 3Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, The Netherlands.
J Infect Dis ; 203(1): 122-30, 2011 Jan 01.
Article em En | MEDLINE | ID: mdl-21148505
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, TNFα, IL-17, and IFNγ. 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 IFNγ 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Calcitriol / Candida albicans / Citocinas / Fatores Imunológicos Limite: Adult / Humans / Male / Middle aged Idioma: En Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Calcitriol / Candida albicans / Citocinas / Fatores Imunológicos Limite: Adult / Humans / Male / Middle aged Idioma: En Ano de publicação: 2011 Tipo de documento: Article