Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3

• Published in: PloS one Vol. 6; no. 6; p. e21674
• Main Authors: Nelson, Corwin D, Nonnecke, Brian J, Reinhardt, Timothy A, Waters, W. Ray, Beitz, Donald C, Lippolis, John D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2011; Public Library of Science (PLoS)
• Subjects: 25-hydroxycholecalciferol; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Agriculture; Animal diseases; Animals; Antigens; Autoimmune diseases; B-lymphocytes; Bacillus Calmette-Guerin vaccine; BCG; BCG vaccine; Biochemistry; Biology; Biophysics; blood cells; Calcifediol - metabolism; Calcitriol; Cattle; CD14 antigen; CD3 antigen; Cell activation; Cells, Cultured; cultured cells; Cytokines; Endocrine system; Enzymes; Flow cytometry; Gene expression; Hydroxylase; Immune response; Immune system; immunity; Immunoglobulin M; Immunology; Infections; Inflammation; Innate immunity; Interferon; Interferon-gamma - metabolism; interferons; interleukins; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphocytes; Lymphocytes B; Lymphocytes T; Macrophages; Male; Medicine; Metabolism; Molecular biology; Monocytes; Multiple sclerosis; Mycobacterium bovis; Mycobacterium bovis - immunology; Nitric Oxide - metabolism; Paracrine signalling; Peripheral blood mononuclear cells; Rodents; Skin cancer; Surface markers; T-lymphocytes; Tuberculin; Tuberculosis; Vaccination; Veterinary Science; Vitamin D; Vitamin D3; Vitamin deficiency; γ-Interferon; United States > US; Iowa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0021674

The active vitamin D metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)(2)D(3) from 25-hydroxyvitamin D(3) (25(OH)D(3)) by the enzyme 1α-hydroxylase in monocytes upon activation by TLR signaling has been found to regulate innate immune responses of monocytes in an intracrine fashion. In this study we wanted to determine what cells expressed 1α-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D(3) to 1,25(OH)(2)D(3) in PBMC cultures regulated antigen-specific immune responses. Initially, we found that stimulation of PBMCs from animals vaccinated with Mycobacterium bovis (M. bovis) BCG with purified protein derivative of M. bovis (M. bovis PPD) induced 1α-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D(3) down-regulated IFN-γ and IL-17F gene expression. Next, we stimulated PBMCs from M. bovis BCG-vaccinated and non-vaccinated cattle with M. bovis PPD and sorted them by FACS according to surface markers for monocytes/macrophages (CD14), B cells (IgM), and T cells (CD3). Sorting the PBMCs revealed that 1α-hydroxylase expression was induced in the monocytes and B cells, but not in the T cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D(3) down-regulated antigen-specific IFN-γ and IL-17F responses in the T cells, even though 1α-hydroxylase expression was not induced in the T cells. Based on evidence of no T cell 1α-hydroxylase we hypothesize that activated monocytes and B cells synthesize 1,25(OH)(2)D(3) and that 1,25(OH)(2)D(3) down-regulates antigen-specific expression of IFN-γ and IL-17F in T cells in a paracrine fashion.