The Bovine Tuberculoid Granuloma

Abstract

The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.

Vaccine-Induced Subcutaneous Granulomas in Goats Reflect Differences in Host–Mycobacterium Interactions between BCG- and Recombinant BCG-Derivative Vaccines

“…Histological examination confirmed the characteristic organization of tuberculous granulomas with central, partly calcified necrosis surrounded by an inflammatory cell infiltrate and a fibrous capsule. This is in accordance with the description of BCG-induced granulomas in goats [ 26 ] and tuberculous granulomas in goats [ 4 , 26 ], cattle [ 16 ] and humans [ 15 ]. Following the commonly used classification scheme for bovine tuberculosis [ 42 ], all granulomas were type 3 granulomas.…”

“…Thus, subcutaneous vaccine granulomas in goats are a highly reproducible model for tuberculous granulomas. The complex organization of these dynamic structures reflects multiple interactions between mycobacteria, their target cells as well as non-specific and specific components of the host immune system [ 12 , 15 , 16 , 53 , 54 ].…”

“…In an in vitro human granuloma model, the differentiation of macrophages into foam cells was induced by oxygenated mycolic acids from M. tuberculosis [ 57 ]. Increased lipid metabolism was also demonstrated in cells surrounding the caseum in human tuberculous granulomas [ 62 ] but is not consistently seen in bovine granulomas [ 16 ]. Not all mycobacteria are able to modify the metabolism of macrophages: M. tuberculosis and M. avium , but not M. smegmatis , induce foam cells [ 57 ].…”

“…Granulomas are characteristic lesions of tuberculosis (TB) developed during the interaction between host cells and mycobacteria to prevent disease progression. At the same time, these cellular aggregates can provide a niche for the pathogen`s survival [ 4 , 15 , 16 ]. Studying granuloma progression and formation in experimental animal TB models including rodents, guinea pig, ruminants and non-human primates allows for insights into these complex processes [ 17 ].…”

Comparison of interferon gamma release assay and CXCL9 gene expression assay for the detection of Mycobacterium bovis infection in African lions (Panthera leo)

“…A previous study has also shown that in lions, there was greater upregulation of CXCL9 than either IFN-g or CXCL10 (Olivier et al, 2015). During M. bovis infection, IFN-g promotes cell-mediated immune responses by activating macrophages and granuloma formation (Silva Miranda et al, 2012;Palmer et al, 2022). Additionally, IFN-g, which is essential for the expression of CXCL9 and CXCL10 by macrophages and several cell types during the recruitment of T-cells at the site of infection, is produced to enhance host protection (Algood et al, 2003; TABLE 1 Results of mycobacterial culture confirmed Mycobacterium bovis infected and uninfected African lions using the QuantiFERON ® -TB Gold Plus (QFT) Mabtech Cat interferon gamma release assay (IGRA) and QFT CXCL9 gene expression assay (GEA).…”