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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #142333


item Waters, Wade
item Palmer, Mitchell
item Nonnecke, Brian
item Whipple, Diana
item Horst, Ronald

Submitted to: Microbial Pathogenesis
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/8/2003
Publication Date: 1/1/2004
Citation: Waters, W.R., Palmer, M.V., Nonnecke, B.J., Whipple, D.L., Horst, R.L. 2004. Mycobacterium bovis infection of vitamin d-deficient nos -/- mice. Microbial Pathagenesis. 36:11-17.

Interpretive Summary: Tuberculosis of cattle persists within the United States causing serious negative economic impacts on the cattle industry due to loss in trade, movement restrictions, and costs associated with tuberculosis testing and surveillance. 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, mice were used as model of tuberculosis infection to determine specific responses (i.e., killing mechanisms) to the organism that causes bovine tuberculosis. Knowledge obtained from this study will assist in the development of new reagents and methods for the detection of tuberculosis of cattle.

Technical Abstract: Vitamin D deficiency is associated with an increased risk for tuberculosis infection. Studies using in vitro systems indicate that 1,25-dihydroxyvitamin D3 [i.e., 1,25(OH)2D3], the most active form of the vitamin, enhances mycobacterial killing by increasing nitric oxide (NO) production. To evaluate concurrently the role of 1,25(OH)2D3 and NO on the host response to tuberculosis infection, mice deficient in NO synthase 2 (NOS2**-/-) and/or vitamin D were aerosol-challenged with Mycobacterium bovis and subsequently evaluated for mycobacterial colonization and lesion formation. Infected NOS2-/- mice developed severe necrotizing pyogranulomatous inflammation of the lungs with heavy M. bovis colonization and systemic dissemination of the bacillus. Colonization and lung lesion area of NOS2**-/- mice exceeded that of NOS2**+/+ mice. Additionally, disease progression was more rapid in NOS2**-/- mice than in NOS2**+/+ mice. Lung colonization and lesion area of vitamin D deficient mice exceeded that of vitamin D replete mice, regardless of NOS2 phenotype. However, effects of vitamin D on colonization, but not lesion area, were more pronounced in NOS2**+/+ mice than in NOS2**-/- mice. These findings are consistent with the current hypothesis that 1,25(OH)2D3 enhances mycobacterial killing through a NO-dependent mechanism. Since responses of NOS2**-/- mice were affected by 1,25(OH)2D3 deficiency, albeit to a lesser extent than were those of NOS2**+/+ mice, NO-independent actions of 1,25(OH)2D3 also likely exist.