Submitted to: PLoS One
Publication Type: Peer reviewed journal
Publication Acceptance Date: 6/15/2011
Publication Date: 6/20/2011
Citation: Nelson, C.D., Nonnecke, B.J., Reinhardt, T.A., Waters, W.R., Beitz, D.C., Lippolis, J.D. 2011. Regulation of Mycobacterium-specific mononuclear cell responses by 25-hydroxyvitamin D3. PLoS One. 6(6):e21674. Available: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021674. Interpretive Summary: This paper highlights the important role of vitamin D in the response to a bacterial infection. Vitamin D plays an important role in gene regulation in bovine immune cells. We show the effect of vitamin D on gene expression in monocytes, B-cells, and T-cells. Also, we show that the effect of vitamin D on these different immune cell types differs. Our data suggests that these different responses to vitamin D may affect the overall immune response.
Technical Abstract: The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), has been shown to be an important regulator of innate and adaptive immune function. In addition, synthesis of 1,25(OH)2D3 from 25-hydroxyvitamin D3 (25[OH]D3) by the enzyme 1alpha-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 1alpha-hydroxylase in stimulated peripheral blood mononuclear cell (PBMC) cultures and if conversion of 25(OH)D3 to 1,25(OH)2D3 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 1alpha-hydroxylase gene expression and that treatment with a physiological concentration of 25(OH)D3 down-regulated IFN-gamma 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 1alpha-hydroxylase expression was induced in the monocytes and B-cells, but not in the T-cells. Furthermore, treatment of stimulated PBMCs with 25(OH)D3 down-regulated antigen-specific IFN-gamma and IL-17F responses in the T-cells, even though 1alpha-hydroxylase expression was not induced in the T-cells. Based on evidence from this study we hypothesize that activated monocytes and B-cells synthesize 1,25(OH)2D3 and that 1,25(OH)2D3 from the monocytes and B-cells down-regulates antigen-specific expression of IFN-gamma and IL-17F in T-cells in a paracrine fashion.