Evaluating natural killer cells’ role in immunological responses to the Bacillus Calmette-Guérin vaccine for bovine tuberculosis

Abstract

Tuberculosis (TB), particularly caused by Mycobacterium tuberculosis and Mycobacterium bovis, remains a leading cause of death worldwide, posing significant challenges in both human and veterinary medicine. Control measures are complicated by the disease's latent potential and the varied effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine, the primary prophylactic against TB. This research aims to evaluate the role of natural killer (NK) cells in immunological responses to the BCG vaccine in the context of bovine tuberculosis (bTB), a significant concern in both agricultural and public health sectors. Special attention is given to exploring how NK cells interact with the BCG vaccine to elicit protective immune responses, potentially influencing vaccine efficacy.

The thesis investigates two core hypotheses: firstly, that NK and NKT cells are crucial to the immune response triggered by BCG vaccination; secondly, that functional bovine NK (bNK) cells can be cultivated from embryonic stem cells (ESCs). These investigations are conducted through a series of advanced methodologies, including flow cytometry to characterize cell populations pre- and post-vaccination and molecular biology techniques such as qPCR to assess the hematopoietic potential and differentiation into NK cells.

Our findings are expected to deepen the understanding of NK cells in the immune landscape of TB, particularly offering insights into their enhancement of immune defenses in vaccination contexts. This study's outcomes may inform strategies to improve the efficacy of BCG vaccination and advance the broader field of infectious disease control within the One Health framework. Adopting this approach underscores the interconnected health of humans, animals, and ecosystems, emphasizing the crucial nature of cross-disciplinary research in addressing global health challenges like tuberculosis.