Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2006
Publication Date: 6/1/2006
Citation: Waters, W.R., Palmer, M.V., Thacker, T.C., Payeur, J.B., Harris, N.B., Minion, F.C., Greenwald, R., Esfandiari, J., Andersen, P., Mcnair, J. 2006. Immune Responses to Defined Antigens of Mycobacterium bovis in Cattle Experimentally Infected with Mycobacterium kansasii. Clinical and Vaccine Immunology. 13(6):611-619. Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in Michigan, California, Texas, and New Mexico demonstrate that the disease is far from eliminated from the United States. Improved techniques are needed for detection of infected cattle. To develop improved tests, it is beneficial to first understand the immune response to infection. In this study, specific host responses of cattle to tuberculosis infection were determined and compared to responses by cattle infected with a similar bacterium. Results from this study demonstrate that additional tools will need to be developed to differentiate infection with these two bacteria. Knowledge obtained from this study will enable more accurate detection of cattle with tuberculosis.
Technical Abstract: Cross-reactive responses elicited by exposure to non-tuberculous mycobacteria often confound interpretation of traditional ante-mortem tests of Mycobacterium bovis infection of cattle. Use of specific proteins (e.g., ESAT-6, CFP-10, and MPB83), however, generally enhances the specificity of bovine tuberculosis tests. While these proteins are absent from many environmental non-tuberculous mycobacteria, they are present in M. kansasii. Instillation of M. kansasii (4 x 10**8 cfu) into the tonsillar crypts of calves elicited delayed type hypersensitivity and in vitro interferon-' and nitrite responses by leukocytes to M. avium and M. bovis purified protein derivative (PPD). While responses by M. kansasii-inoculated calves to M. avium and M. bovis PPD were approximately equivalent, responses by M. bovis-inoculated calves (4 x 10**4 cfu intratonsilarly) to M. bovis PPD exceeded (P < 0.05) respective responses to M. avium PPD. Interferon-gamma and nitrite responses by M. kansasii-inoculated calves to rESAT-6:CFP-10 exceeded (P < 0.05) corresponding responses by non-inoculated calves as early as 15 and 30 days after inoculation, respectively, and persisted throughout the study. Interferon-gamma and nitrite responses by M. bovis-inoculated calves to rESAT-6:CFP-10 exceeded (P < 0.05) corresponding responses by M. kansasii-inoculated calves beginning 30 days after inoculation. Using a lipoarabinomannan-based enzyme-linked immunosorbent assay, specific serum antibodies were detected as early as 50 days after challenge with M. kansasii. By multi-antigen print immunoassay and immunoblot, specific antibodies to MPB83, but not ESAT-6 or CFP-10, were detected in sera from M. kansasii-inoculated calves; however, antibody responses to MPB83 were notably weak as compared to those elicited by M. bovis infection. These findings indicate that M. kansasii infection of calves elicits specific responses that may confound interpretation of bovine tuberculosis tests.