Document Detail


1,25-dihydroxyvitamin D3 modulates cytokine production induced by Candida albicans: impact of seasonal variation of immune responses.
MedLine Citation:
PMID:  21148505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ai-Leng Khoo; Louis Y A Chai; Hans J P M Koenen; Bart-Jan Kullberg; Irma Joosten; André J A M van der Ven; Mihai G Netea
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  203     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-01-11     Revised Date:  2012-01-02    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  122-30     Citation Subset:  AIM; IM    
Affiliation:
Department of Laboratory Medicine, Radboud University Nijmegen Medical Center; 3Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Calcitriol / pharmacology*
Candida albicans / immunology*
Cells, Cultured
Cytokines / secretion*
Flow Cytometry
Gene Expression Profiling
Human Experimentation
Humans
Immunologic Factors / pharmacology*
Lectins, C-Type / analysis
Leukocytes, Mononuclear / chemistry,  drug effects,  immunology,  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 Proteins / analysis
Toll-Like Receptor 2 / analysis
Toll-Like Receptor 4 / analysis
Chemical
Reg. No./Substance:
0/Cytokines; 0/Immunologic Factors; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Membrane Proteins; 0/Nerve Tissue Proteins; 0/Receptors, Cell Surface; 0/SOCS1 protein, human; 0/SOCS3 protein, human; 0/Suppressor of Cytokine Signaling Proteins; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/dectin 1; 0/mannose receptor; 32222-06-3/Calcitriol

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