Heterogeneity of pulmonary granulomas in cattle experimentally infected with Mycobacterium bovis

Authors: Palmer, Mitchell; THACKER, TYLER - Animal And Plant Health Inspection Service (APHIS); Kanipe, Carly; Boggiatto, Paola

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/8/2021
Publication Date: 5/7/2021
Citation: Palmer, M.V., Thacker, T.C., Kanipe, C.R., Boggiatto, P.M. 2021. Heterogeneity of pulmonary granulomas in cattle experimentally infected with Mycobacterium bovis. Frontiers in Veterinary Science. 8. https://doi.org/10.3389/fvets.2021.671460.
DOI: https://doi.org/10.3389/fvets.2021.671460

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 30, 90, 180 and 270 days after experimental infection and characterized features of disease at the site of infection. It was found that the number of bacteria at individual sites varied significantly. Understanding why the immune response controls bacterial replication at some sites better than others is useful in development of improved diagnostic tests or vaccines.

Technical Abstract: Mycobacterium bovis is the cause of tuberculosis in most animals, most notably cattle. The stereotypical lesion of bovine tuberculosis is the granuloma; a distinct morphological lesion where host and pathogen interact and disease outcome (i.e., dissemination, confinement, or resolution) is determined. Accordingly, it is critical to understand host-pathogen interactions at the granuloma level. Host-pathogen interactions within individual granulomas at different stages of disease have not been examined in cattle. We examined bacterial burden and cytokine expression in individual pulmonary granulomas from steers at 30, 90, 180, and 270 days after experimental aerosol infection with M. bovis. Bacterial burdens within individual granulomas examined 30 days after infection were greater and more heterogenous (variable) than those examined 90 to 270 days after infection. Bacterial burdens did not correlate with expression of IFN-gamma, TNF-alpha, TGF-beta, granuloma stage, or lung lesion score, although there was a modest positive correlation with IL-10 expression. Granuloma stage did have modest positive and negative correlations with TNF-alpha and IL-10, respectively. Heterogeneity and mean expression of IFN-gamma, IL-10 and TNF-alpha did not differ significantly over time, however, expression of TGF-beta at 90 days was significantly greater than that seen at 30 days after infection.