TB Compare – Discovery of novel protective immune responses against zoonotic bovine and human tuberculosis
Parasitology and Biology of Tropical Infectious Disease Pathogens
Final Report Abstract
Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (Mtbc), remains a significant global health threat, affecting humans, livestock, and wildlife. Despite advances in medicine, the absence of a universally effective vaccine complicates efforts to control the disease, which continues to result in millions of new cases and deaths annually. The economic impact on the livestock industry, especially through bovine tuberculosis, adds to the urgency of finding effective control mechanisms. A key challenge in combating TB is the limited understanding of immune mechanisms that effectively control and eliminate the bacteria. The existing Bacillus Calmette-Guérin (BCG) vaccine provides variable protection, highlighting the need for new strategies based on a deeper understanding of the immune response to Mtbc. This project sought to enhance our understanding of how different mammals' immune systems respond to Mtbc, focusing on the role of Interferon gamma (IFNγ) in activating macrophages, the primary host cells of Mtbc. Our research revealed species-specific responses to IFNγ and Mtbc infection, particularly in the activation and effectiveness of the inducible nitric oxide synthase (iNOS) pathway, which plays a crucial role in controlling Mtbc intracellular growth in mice but appears less central in humans and cattle. Our findings underscore the complexity of the immune response to TB across different species and highlight the potential for species-specific strategies to enhance TB control. By comparing immune responses in mice, cattle, and humans, we identified key differences in the regulation and effectiveness of IFNγ-induced defenses, including the varied role of iNOS in controlling Mtbc growth. This research contributes to the broader understanding of TB immunology and opens pathways for developing more effective vaccines and therapeutic strategies tailored to the specific immune mechanisms of different hosts.
Publications
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Tobacco smoke exposure recruits inflammatory airspace monocytes that establish permissive lung niches for Mycobacterium tuberculosis. Science Translational Medicine, 15(725).
Corleis, Björn; Tzouanas, Constantine N.; Wadsworth, Marc H.; Cho, Josalyn L.; Linder, Alice H.; Schiff, Abigail E.; Zessin, Björn; Stei, Fabian; Dorhoi, Anca; Dickey, Amy K.; Medoff, Benjamin D.; Shalek, Alex K. & Kwon, Douglas S.
