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

J Infect Dis. 2011 Jan 1;203(1):122-30. doi: 10.1093/infdis/jiq008.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcitriol / pharmacology*
  • Candida albicans / immunology*
  • Cells, Cultured
  • Cytokines / metabolism*
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Immunologic Factors / pharmacology*
  • Lectins, C-Type / analysis
  • Leukocytes, Mononuclear / chemistry
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / microbiology
  • Male
  • Mannose-Binding Lectins / analysis
  • Membrane Proteins / analysis
  • Middle Aged
  • Nerve Tissue Proteins / analysis
  • Receptors, Cell Surface / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seasons
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins / analysis
  • Toll-Like Receptor 2 / analysis
  • Toll-Like Receptor 4 / analysis

Substances

  • Cytokines
  • Immunologic Factors
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • SOCS1 protein, human
  • SOCS3 protein, human
  • Suppressor of Cytokine Signaling 1 Protein
  • Suppressor of Cytokine Signaling 3 Protein
  • Suppressor of Cytokine Signaling Proteins
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • dectin 1
  • mannose receptor
  • Calcitriol