Location: Infectious Bacterial Diseases ResearchTitle: Emerging understanding of tuberculosis and the granuloma by comparative analysis in humans, cattle, zebrafish and non-human primates
Submitted to: Veterinary Pathology
Publication Type: Review Article
Publication Acceptance Date: 5/6/2017
Publication Date: 1/10/2018
Citation: Palmer, M.V. 2018. Emerging understanding of tuberculosis and the granuloma by comparative analysis in humans, cattle, zebrafish and non-human primates. Veterinary Pathology. 55(1):8-10. https://doi.org/10.1177/0300985817712795.
Technical Abstract: The granuloma is the hallmark lesion of tuberculosis in man and animals. It is here that the host interacts with the pathogen and disease outcomes are determined. Paradoxically, the granuloma is essential for control of mycobacterial pathogens, yet the granuloma also provides a venue for bacterial survival, multiplication, latency and dissemination. Animal models of human tuberculosis such as the mouse, zebrafish and non-human primate have added to our understanding of the granuloma and its role in tuberculosis pathogenesis. New findings in these models show the granuloma to be dynamic and that granulomas develop independently of each other, even within the same organ in the same host. It is clear that to fully understand the pathogenesis of tuberculosis, interactions must be examined at the level of the granuloma. Studies of granulomas in bovine tuberculosis have shown the important roles of CD4+, CD8+ and gamma/delta T-cells in granuloma formation as well as the production of inflammatory cytokines such as IFN-gamma, TNF-alpha and IL-17A, and anti-inflammatory cytokines such as IL-10 and TGF-beta. More recent studies have shown that granulomas of similar microscopic morphology, within the same organ, may differ in cytokine gene expression profiles. Newer approaches, such as gene expression analysis and proteomics, combined with anatomic pathology, will further the investigation of microbial offense and host defense at the granuloma level. Such work will not only further our understanding of tuberculosis pathogenesis, but also aid in developing enhanced diagnostic assays and efficacious vaccines for both humans and animals.