Early pulmonary lesions in cattle infected via aerosolized Mycobacterium bovis

Authors: Palmer, Mitchell; Wiarda, Jayne; KANIPE, CARLY - US Department Of Agriculture (USDA); Thacker, Tyler

Submitted to: Veterinary Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/9/2019
Publication Date: 3/21/2019
Citation: Palmer, M.V., Wiarda, J.E., Kanipe, C., Thacker, T.C. 2019. Early pulmonary lesions in cattle infected via aerosolized Mycobacterium bovis. Veterinary Pathology. 56(4). https://doi.org/10.1177%2F0300985819833454.
DOI: https://doi.org/10.1177%2F0300985819833454

Interpretive Summary: The bacterium, Mycobacterium bovis causes tuberculosis in most animal including humans. The disease caused by M. bovis can be indistinguishable from that caused by M. tuberculosis, the more common cause of tuberculosis in humans. Cattle have sometimes been used as models to study human tuberculosis. Although both M. bovis and M. tuberculosis have existed for thousands of years, tuberculosis is still the leading cause of death to infectious disease. It is believed that understanding interactions of the bacteria with host tissues at the site of infection is critical to understanding tuberculosis. We examined cattle early (15 and 30 days) after experimental infection and characterized features of early disease at the site of infection. It was found that early events in cattle tuberculosis parallel many early events reported for human tuberculosis. Cattle may serve as useful models of human tuberculosis in development of improved diagnostic tests or vaccines.

Technical Abstract: Mycobacterium bovis is a serious zoonotic pathogen and the cause of tuberculosis in many animal species, most notably, cattle. The hallmark lesion of tuberculosis is the granuloma. It is within the developing granuloma that host interacts with pathogen; therefore, it is critical to understand host-pathogen interactions at the granuloma level. Cytokines and chemokines drive cell recruitment, activity, function and ultimately determine the success or failure of the host to control infection. In calves, early lesions, (i.e., 15 and 30 days) after experimental aerosol infection were examined microscopically using in situ hybridization and immunohistochemistry to demonstrate early infiltrates of CD68+ macrophages within alveoli and alveolar interstitium, as well as the presence of CD4, CD8 and gamma/delta T-cells. Unlike lesions at 15 days, lesions at 30 days after infection contained small foci of necrosis among infiltrates of macrophages, lymphocytes and multinucleated giant cells and increased numbers of acid-fast bacilli within necrotic areas. At both timepoints, there was abundant expression of the chemokines CXCL9, MCP-1/CCL2 and the cytokine TGF-beta. The proinflammatory cytokines TNF-alpha and IL-1beta and the anti-inflammatory cytokine, IL-10 were expressed at moderate levels at both timepoints, while expression of IFN-gamma was limited. These findings document the early pulmonary lesions after exposure to M. bovis infection in calves and are in general agreement with the proposed pathogenesis of tuberculosis described in laboratory animal and non-human primate models of tuberculosis.