Measuring bovine gamma delta T cell function at the site of Mycobacterium bovis infection

Authors: RUSK, RACHEL - Kansas State University; Palmer, Mitchell; Waters, Wade; MCGILL, JODI - Kansas State University

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2017
Publication Date: 12/1/2017
Citation: Rusk, R.A., Palmer, M.V., Waters, W.R., McGill, J.L. 2017. Measuring bovine gamma delta T cell function at the site of Mycobacterium bovis infection. Veterinary Immunology and Immunopathology. 193-194:38-49. https://doi.org/10.1016/j.vetimm.2017.10.004.
DOI: https://doi.org/10.1016/j.vetimm.2017.10.004

Interpretive Summary: Despite highly successful eradication efforts in several countries, tuberculosis of cattle remains a serious health concern worldwide. In addition, recent outbreaks of tuberculosis in Texas, New Mexico, Indiana, California, and South Dakota as well as recurrence of infection in Michigan demonstrate that the disease is far from eliminated from the United States. Improved techniques are needed for detection of infected cattle as well as improved control strategies (e.g., vaccines). To develop improved tests and vaccines, it is beneficial to first understand the nature of bovine immune responses to the pathogen. In this study, important cell types of cattle involved in the immune response to bovine tuberculosis were characterized; both at the site of infection and in blood samples collected from infected animals. In addition, specific mediators of the response were identified. This basic information will be useful for development of improved tests and vaccines for the control of tuberculosis in cattle.

Technical Abstract: Bovine gamma delta T cells are amongst the first cells to accumulate at the site of Mycobacterium bovis infection; however, their role in the developing lesion remains unclear. We utilized transcriptomics analysis, in situ hybridization, and a macrophage/gamma delta T cell co-culture system to elucidate the role of gamma delta T cells in local immunity to M. bovis infection. Transcriptomics analysis revealed that gamma delta T cells upregulated expression of several novel, immune-associated genes in response to stimulation with M. bovis antigen. BCG-infected macrophage/gamma delta T cell co-cultures confirmed the results of our RNAseq analysis, and revealed that gamma delta T cells from M. bovis-infected animals had a significant impact on bacterial viability. Analysis of gamma delta T cells within late-stage M. bovis granulomas revealed significant expression IFN-gamma and CCL2, but not IL-10, IL-22, or IL-17. Our results suggest gamma delta T cells influence local immunity to M. bovis through cytokine secretion and direct effects on bacterial burden.