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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #124644

Title: MODULATION OF MYCOBACTERIUM BOVIS SPECIFIC RESPONSES OF BOVINE PERIPHERAL BLOOD MONONUCLEAR CELLS BY 1,25-DIHYDROXYVITAMIN D**3

Author
item Waters, Wade
item Nonnecke, Brian
item Palmer, Mitchell
item Whipple, Diana
item 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/A

Interpretive 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.