Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2013
Publication Date: N/A
Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, an outbreak of tuberculosis in white-tailed deer in Michigan and continued importation of tuberculous cattle from Mexico have seriously hindered eradication efforts within the United States. Without new strategies, eradication and control of bovine tuberculosis will be impossible. Thus, improved techniques for control, such as better diagnostic tests and vaccines, are needed for prevention of tuberculosis in cattle. In this article, immune mechanisms associated with bovine tuberculosis infection and vaccination are reviewed and compared to similar studies on human tuberculosis. This article provides a summary on the current knowledge of bovine tuberculosis research and its relevance to human tuberculosis. Additionally, it provides insight into the “One Health” principle using bovine tuberculosis as a primary example for this approach.
Technical Abstract: Pioneer studies on infectious disease and immunology by Jenner, Pasteur, Koch, Von Behring, Nocard, Roux, and Ehrlich forged a path for the dual-purpose with dual benefit approach, demonstrating a profound relevance of veterinary studies for biomedical applications. Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is an exemplary model for the demonstration of this concept. Early studies with cattle were instrumental in the development of the use of Koch’s tuberculin as an in vivo measure of cell-mediated immunity for diagnostic purposes. Calmette and Guerin demonstrated the efficacy of an attenuated M. bovis strain (BCG) in cattle prior to use of this vaccine in humans. The interferon-gamma release assay, now widely used for TB diagnosis in humans, was developed circa 1990 for use in the Australian bovine TB eradication program. More recently, M. bovis infection and vaccine efficacy studies with cattle have demonstrated a correlation of vaccine-elicited T cell central memory (TCM) responses to vaccine efficacy, correlation of specific antibody to mycobacterial burden and lesion severity, and detection of antigen-specific IL-17 responses to vaccination and infection. Additionally, positive prognostic indicators of bovine TB vaccine efficacy (i.e., responses measured after infection) include: reduced antigen-specific IFN-gamma, iNOS, IL-4, and MIP1-alpha responses; reduced antigen-specific expansion of CD4+ T cells; and a diminished activation profile on T cells within antigen stimulated cultures. Delayed type hypersensitivity and IFN-gamma responses correlate with infection but do not necessarily correlate with lesion severity whereas antibody responses generally correlate with lesion severity. Recently, antibody-based tests have emerged for use in the detection of tuberculous animals, particularly elephants, captive cervids, and camelids. Additionally, B cell aggregates are consistently detected within tuberculous lesions of humans, cattle, mice and various other species, indicating a role for B cells in the immunopathogenesis of TB. Comparative immunology studies including partnerships of researchers with veterinary and medical perspectives will continue to provide mutual benefit to TB research in man and animals.