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Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1204-1212, Vol. 8, No. 6
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.6.1204-1212.2001

Modulation of Mycobacterium bovis-Specific Responses of Bovine Peripheral Blood Mononuclear Cells by 1,25-Dihydroxyvitamin D3

W. R. Waters,1,* B. J. Nonnecke,2 T. E. Rahner,1 M. V. Palmer,1 D. L. Whipple,1 and R. L. Horst2

Bacterial Diseases of Livestock Research Unit1 and Periparturient Diseases of Livestock Research Unit,2 National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, Iowa 50010-0070

Received 8 May 2001/Returned for modification 17 July 2001/Accepted 7 August 2001

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 antitubercular 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 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 gamma interferon (IFN-gamma ) 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 antimicrobial mechanism of activated macrophages, and suggest that 1,25(OH)2D3 limits host damage by decreasing M. bovis-induced IFN-gamma production.

* Corresponding author. Mailing address: United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Bacterial Diseases of Livestock Research Unit, 2300 Dayton Ave., P.O. Box 70, Ames, IA 50010-0070. Phone: (515) 663-7756. Fax: (515) 663-7458. E-mail: rwaters{at}nadc.ars.usda.gov.

Clinical and Diagnostic Laboratory Immunology, November 2001, p. 1204-1212, Vol. 8, No. 6
1071-412X/01/$04.00+0   DOI: 10.1128/CDLI.8.6.1204-1212.2001


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