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Title:   Author  item
                                            Waters, Wadeitem
                                            Nonnecke, Brianitem
                                            Palmer, Mitchellitem
                                            Whipple, Dianaitem
                                            Horst, Ronald
  Submitted to: Clinical and Diagnostic Laboratory Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 8/13/2001
                                    Publication  Date: N/A
                                    Citation: N/AInterpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, a recent outbreak of tuberculosis in white-tailed deer in Michigan has seriously hindered eradication efforts within the United States. Improved techniques are needed for detection of infected cattle.  To develop improved diagnostics, it is beneficial to understand the immune response of cattle to tuberculosis infection. In this study, specific effects of vitamin D on the immune response of tuberculous cattle were determined. Knowledge obtained from this study will assist in the development of new reagents and methods for the detection of tuberculosis of cattle.
                                Technical Abstract: Historically, administration of vitamin D has been considered beneficial in the treatment of tuberculosis. The interaction of this vitamin [i.e 1,25-dihdroxyvitamin D3 (1,25(OH)2D3)] with the anti-tubercular immune response, however, is not clear. In the present study, in vitro recall responses of peripheral blood mononuclear cells (PBMC) from cattle  infected with Mycobacterium bovis (M. bovis) were used to study the immune modulatory effects of 1,25(OH)2D3 on M. bovis-specific responses in vitro. Addition of 1 or 10 nM 1,25(OH)2D3 inhibited M. bovis-specific proliferative responses of PBMC from M. bovis-infected cattle, affecting predominately the CD4+ cell subset. In addition, 1,25(OH)2D3 inhibited M. bovis-specific interferon-g (IFN-g) production yet enhanced M. bovis-specific nitric oxide (NO) production. Lymphocyte apoptosis, measured by flow cytometry using annexin-V staining, was diminished by  addition of 1,25(OH)2D3 to PBMC cultures. These findings support the current hypothesis that 1,25(OH)2D3 enhances mycobacterial killing by increasing NO production, a potent anti-microbial mechanism of activated macrophages, and suggest that 1,25(OH)2D3 limits host damage by decreasing M. bovis-induced IFN-g production.


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