Enhanced detection of Mycobacterium bovis-specific T cells in experimentally-infected cattle

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

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2021
Publication Date: 7/14/2021
Citation: Boggiatto, P.M., Kanipe, C.R., Palmer, M.V. 2021. Enhanced detection of Mycobacterium bovis-specific T cells in experimentally-infected cattle. Frontiers in Veterinary Science. https://doi.org/10.3389/fvets.2021.676710.
DOI: https://doi.org/10.3389/fvets.2021.676710

Interpretive Summary: Bovine tuberculosis is a disease of cattle caused by infection with Mycobacterium bovis. This bacteria not only affects cattle, resulting in production losses and economic hardship to producers world wide, it is also a public health concern as it is capable of infecting humans and causing disease. Despite eradication efforts, bovine tuberculosis continues to be a problem due in part to our lack of efficacious vaccines, our inability to detect infected animals early in disease, and wild life reservoirs. In order to develop improved vaccines and diagnostic methods, a fundamental understanding of protective immune responses is needed. T cells, a type of white blood cells, plays a major role in the response to tuberculosis, and are at the center of many studies. The methods presented in this manuscript, allow for the concurrent characterization of functional abilities for T cells responding to M. bovis infection, and may allow us to further understand cattle immune response to bovine tuberculosis. The work presented here will be of interest to researchers in the field of tuberculosis as well as others studying infectious diseases of cattle.

Technical Abstract: Bovine tuberculosis (bTB), caused by infection with Mycobacterium bovis, continues to be a major economic burden associated with production losses and a public health concern due to its zoonotic nature. As with other intracellular pathogens, cell-mediated immunity plays an important role in the control of infection. Characterization of such responses is important for understanding the immune status of the host, and to identify mechanisms of protective immunity or immunopathology. This type of information can be important in the development of vaccination strategies, diagnostic assays, and in predicting protection or disease progression. However, the frequency of circulating M. bovis-specific T cells are often low, making the analysis of such responses difficult. As previously demonstrated in a different cattle infection model, antigenic expansion allows us to increase the frequency of antigen-specific T cells. Moreover, the concurrent assessment of cytokine production and proliferation provides a deeper understanding of the functional nature of these cells. The work presented here, analyzes the T cell response following experimental M. bovis infection in cattle via in vitro antigenic expansion and re-stimulation to characterize antigen-specific CD4, CD8 and gamma delta T cells and their functional phenotype, shedding light on the variable functional ability of these cells. Data gathered from these studies can help us better understand the cellular response to M. bovis infection and develop improved vaccines and diagnostic tools.