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Title:   Author  item
                                            Waters, Wadeitem
                                            HOPE, JAYNE - University Of Edinburghitem
                                            HAMILTON, CARLY - University Of Edinburghitem
                                            Palmer, Mitchellitem
                                            MCNAIR, JAMES - Agri-Food And Biosciences Instituteitem
                                            SKUCE, ROBIN - Agri-Food And Biosciences Instituteitem
                                            ALLEN, ADRIAN - Queens University - United Kingdomitem
                                            BUDDLE, BRYCE - Agresearchitem
                                            VILLARREAL-RAMOS, BERNARDO - Veterinary Laboratories Agency (VLA)item
                                            VORDERMEIER, H - Veterinary Laboratories Agency (VLA)
  Submitted to: Book Chapter
                                    Publication Type: Book / Chapter
                                    Publication Acceptance Date: 2/25/2014
                                    Publication  Date: 9/28/2015
                                    Citation: Waters, W.R., Hope, J.C., Hamilton, C.A., Palmer, M.V., Mcnair, J., Skuce, R.A., Allen, A.A., Buddle, B.M., Villarreal-Ramos, B., Vordermeier, H.M. 2015. Immunopathogenesis of Mycobacterium bovis infection of cattle. In: Mukundan, M., Chambers, M. Waters, R., Larsen, M., editors. Tuberculosis, Leprosy, and Mycobacterial Diseases of Man and Animals: The Many Hosts of Mycobacteria. Boston, MA: Centre for Agriculture and Biosciences International. p. 136-167.Interpretive Summary:
                                Technical Abstract: Aerosol and intratracheal inoculation routes are commonly used for experimental biology purposes to infect cattle with virulent Mycobacterium bovis, each resulting primarily in a respiratory tract infection including lungs and lung-associated lymph nodes.  Disease severity is dose and time dependent, closely mimicking natural infection of cattle. Additionally, unique insights into M. bovis transmission have been gained through ‘in contact’ studies in which sentinel cattle are exposed to M. bovis-infected cattle in a model of natural infection. Experimental approaches permit disease confirmation through postmortem examination with laboratory analysis by histopathology and bacterial culture, defining the relationship between dose and route of infection, immune response, and the pathogenesis of infection. Also, access to naturally infected cattle provides a unique opportunity to evaluate vaccine and ante-mortem testing strategies, particularly as animals are often available for post-mortem inspection for infection confirmation as well as for gross and microscopic assessment of lesions. Thus, intervention strategies may be directly assessed, as opposed to being inferred based upon immunologic and clinical parameters. Recent studies have clearly demonstrated an association of T cell central memory and IL-17 effector immune responses to vaccine-elicited protection of cattle upon subsequent infection with M. bovis. Additional studies have demonstrated that while gamma delta T cells produce IL-17 in response to various protein and non-protein antigens upon M. bovis infection, CD4 T cells are the primary producers of this key inflammatory cytokine in the response to bovine tuberculosis. Additionally, gamma delta T cells from M. bovis-infected cattle proliferate and produce IFN-gamma in response to a peptide cocktail from immunodominant M. bovis proteins. This chapter covers experimental biology approaches used for the evaluation of the immunopathogenesis of M. bovis infection in cattle, specific details on innate and adaptive immune responses to vaccination/infection, discoveries in host genetic factors to resistance and susceptibility, and aspects of transmission of bovine tuberculosis between cattle and wildlife reservoirs.


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