Histopathologic differences in granulomas of BCG vaccinated and non-vaccinated cattle with bovine tuberculosis

Authors: Kanipe, Carly; Boggiatto, Paola; Putz, Ellie; Palmer, Mitchell

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/24/2022
Publication Date: 11/7/2022
Citation: Kanipe, C.R., Boggiatto, P.M., Putz, E.J., Palmer, M.V. 2022. Histopathologic differences in granulomas of BCG vaccinated and non-vaccinated cattle with bovine tuberculosis. Frontiers in Microbiology. 13, Article 1048648. https://doi.org/10.3389/fmicb.2022.1048648.
DOI: https://doi.org/10.3389/fmicb.2022.1048648

Interpretive Summary: Cattle can become infected with a bacterium which causes tuberculosis. This bacterium can cause disease in people and can cost cattle farmers a lot of money. There is a vaccine for cattle tuberculosis which can reduce the severity of disease, but it is not consistent and does not prevent infection. A problem with this vaccine is that we do not know how it provides protection. One theory is that it changes the composition of the lesions that form. We examined lesions that formed in both vaccinated and non-vaccinated cattle and compared them to each other. Not only did we see fewer lesions in vaccinates, but they were smaller and had less dead tissue. Surprisingly, other components such as the relative rates of severe lesions, and the presence of certain cell types were similar between the two groups. This suggests that the vaccine reduces the number of bacteria which become established and works to keep the lesions that do develop smaller and relatively less severe.

Technical Abstract: Mycobacterium bovis (M. bovis) is the zoonotic bacterium responsible for bovine tuberculosis. An attenuated form of M. bovis, Bacillus Calmette-Guerin (BCG), is a modified live vaccine known to provide variable protection in cattle and other species. Protection for this vaccine is defined as a decrease in disease severity rather than prevention of infection and is determined by evaluation of the characteristic lesion of tuberculosis: the granuloma. Despite its recognized ability to decrease disease severity, the mechanism by which BCG imparts protection remains poorly understood. Understanding the histopathologic differences between granulomas which form in BCG vaccinates compared to non-vaccinates may help identify how BCG imparts protection and lead to an improved vaccine. Utilizing special stains and image analysis software, we examined 88 lymph nodes obtained from BGC-vaccinated and non-vaccinated animals experimentally infected with M. bovis. We evaluated the number of granulomas, their size, severity (grade), density of multinucleated giant cells (MNGC), and the amounts of necrosis, mineralization, and fibrosis. BCG vaccinates had fewer overall and smaller high-grade granulomas with less necrosis than non-vaccinates. The relative number of high- and low- grade lesions was similar as were the amounts of mineralization and the density of MNGC. The amount of fibrosis was higher in low-grade granulomas from vaccinates compared to non-vaccinates. These findings suggest that BCG vaccination reduces bacterial establishment, resulting in the formation of fewer granulomas. In granulomas that form, BCG has a protective effect by containing their size, reducing the relative amount of necrosis, and increasing fibrosis in low-grade lesions. Vaccination does not affect the amount of mineralization or density of MNGC.