Seminar - The Macrophage Awakens: Host-Directed Therapy for Tuberculosis

Sponsored by UBC Department of Microbiology & Immunology

Abstract: Tuberculosis (TB) is a deadly respiratory disease caused by inhaling the bacterium Mycobacterium tuberculosis (Mtb) and is one of the largest disease components of the global antimicrobial resistance crisis that threatens to cause 10 million deaths per year by 2050. Inhaled Mtb are engulfed by immune cells in the lungs called macrophages, which normally kill invading bacteria. However, Mtb reprograms host macrophages to disable their killing ability, allowing the bacteria to remain hidden from the immune response and protected from drug therapy. By targeting host cell proteins rather than the bacterium, host-directed therapy can overcome antibiotic resistance and bacteria-mediated evasion mechanisms, thereby offering unique promise as an alternative treatment for TB. Our research has identified key host proteins and their associated antibacterial functions that are exploited by Mtb to shut down the killing function of macrophages. The discovery of novel and tangible drug targets to boost immunity to TB will facilitate our long-term vision to develop novel drugs that can specifically target these host proteins to advance host-directed therapy for TB.