Modulation of Mycobacterium bovis-specific responses of bovine peripheral blood mononuclear cells by 1,25-dihydroxyvitamin D-3

Historically, administration of vitamin D has been considered beneficial in the treatment of tuberculosis. The interaction of this vitamin {i.e., 1,25 -dihydroxyvitamin D-3 [1,25(OH)(2)D-3]} with the antitubercular immune resp onse, however, is not clear. In the present study, in vitro recall response s of peripheral blood mononuclear cells (PBMC) from cattle infected with My cobacterium bovis were used to study the immune-modulatory effects of 1,25( OH)(2)D-3 on M. bovis-specific responses in vitro. Addition of 1 or 10 nM 1 ,25(OH)(2)D-3 inhibited M. bovis-specific proliferative responses of PBMC f rom M. bovis-infected cattle, affecting predominately the CD4(+) cell subse t. In addition, 1,25(OH)(2)D-3 inhibited M. bovis-specific gamma interferon (IFN-gamma) production yet enhanced M. bovis-specific nitric oxide (NO) pr oduction. 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)(2)D-3 enhances mycob acterial killing by increasing NO production, a potent antimicrobial mechan ism of activated macrophages, and suggest that 1,25(OH)2D3 limits host dama ge by decreasing M. bovis-induced IFN-gamma production.