Tuberculosis: study sheds light on species-specific host-pathogen interactions

A multidisciplinary team led by researchers from The Francis Crick Institute and including University College Dublin, Public Health England, The Animal and Plant Health Agency and the Royal Veterinary College (RVC) has shed new light on how the bacteria that cause tuberculosis (TB) in humans and animals manipulate the host immune system to cause disease. The work is published in PLoS Pathogens.

Supported through a variety of funders including BBSRC (ERADbTB – Eradication of bovine tuberculosis through basic research and discovery scheme), MRC, Wellcome Trust, Cancer Research UK, Science Foundation Ireland, the Francis Crick Institute, and the RVC, over the last three years, the researchers studied how Mycobacterium bovis and Mycobacterium tuberculosis interact with bovine and human macrophages. They discovered that only the infection of bovine macrophages with M. bovis resulted in the formation of multinucleated giant cells (MNGCs), a hallmark of tuberculous pathology. They went on to identify a specific protein of M. bovis, MPB70, and extracellular vesicles from bovine macrophages as mediators of MNGC formation.

The findings implicate multinucleated giant cell formation in the contrasting pathology between human and bovine bacilli in cattle. The study also reveals how a combination of bacterial factors and species-specific immune responses shapes the unique interaction of the pathogen with its host.

The work has implications for understanding how pathogens jump the species barrier and adapt to new hosts, highlighting the power of One Health approaches that employ comparative studies of human and animal pathogens to decipher disease mechanisms.

Article: Queval, C. J., Fearns, A., Botella, L., Smyth, A., Schnettger, L., Mitermite, M., Wooff, E., Villarreal-Ramos, B., Garcia-Jimenez, W., Heunis, T., Trost, M., Werling, D., Salguero, F. J., Gordon, S. V., & Gutierrez, M. G. (2021). Macrophage-specific responses to human- and animal-adapted tubercle bacilli reveal pathogen and host factors driving multinucleated cell formation. PLoS Pathogens, 17(3), e1009410 (advance online publication), doi: 10.1371/journal.ppat.1009410

[SOURCE: Royal Veterinary College]