Histopathologic differences in granulomas of Mycobacterium bovis bacille Calmette Guérin (BCG) vaccinated and non-vaccinated cattle with bovine tuberculosis

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 reduction 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 granulomas overall and smaller high-grade granulomas with less necrosis than non-vaccinates. The relative numbers of high- and low- grade lesions were 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. Collectively, 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 did not affect the amount of mineralization or density of MNGC.

Ability of mycobacterial pathogens to establish a persistent infection is lost by deletion of a single gene,rel, regulator of the stringent response

“…Granuloma formation was not examined in the present study. Studies in cattle have shown granulomas do develop in lungs following experimental infection (50, 51). It was inferred from the study in mice and results from the study with Map that the BCG rel deletion mutant was cleared.…”

Comparative pathology of experimental pulmonary tuberculosis in animal models

“…There have been many studies that have looked at the cellular composition of bovine granulomas experimentally infected with M. bovis. Using techniques such as IHC and in-situ hybridisation (ISH) it has allowed us to characterise, visualise and locate different cell types within the granuloma (5,7,70,(97)(98)(99). CD68 is commonly used to identify macrophages, epithelial cells and MNGCs to help differentiate the different stages of granuloma development (70).…”

Specific and non-specific effects of Mycobacterium bovis BCG vaccination in dairy calves

“…The BCG vaccine has also been studied as a tool for controlling bovine tuberculosis (bTB) (4). While the vaccine is not highly effective in preventing M. bovis infection in cattle, it can provide protection against severe forms of the disease, reducing visible lesions, histopathological changes and the spread of infection (5,6).…”