Mycobacterium bovis is a serious zoonotic pathogen and the cause of
tuberculosis in many mammalian species, most notably, cattle. The hallmark lesion of
tuberculosis is the
granuloma. It is within the developing
granuloma where host and pathogen interact; therefore, it is critical to understand host-pathogen interactions at the
granuloma level.
Cytokines and
chemokines drive cell recruitment, activity, and function and ultimately determine the success or failure of the host to control infection. In calves, early lesions (ie, 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 γδ T cells. Unlike lesions at 15 days, lesions at 30 days after
infection contained small foci of
necrosis among infiltrates of macrophages, lymphocytes, neutrophils, and multinucleated giant cells and extracellular
acid-fast bacilli within necrotic areas. At both time points, there was abundant expression of the
chemokines CXCL9, MCP-1/CCL2, and the
cytokine transforming growth factor (TGF)-β. The proinflammatory
cytokines tumor necrosis factor (TNF)-α and
interleukin (IL)-1β, as well as the anti-inflammatory
cytokine IL-10, were expressed at moderate levels at both time points, while expression of IFN-γ was limited. These findings document the early pulmonary lesions after M. bovis
infection in calves and are in general agreement with the proposed pathogenesis of
tuberculosis described in laboratory animal and nonhuman primate models of
tuberculosis.