Grant: CIHR Fellowship

Ever since the German scientist Robert Koch discovered Mycobacterium tuberculosis (Mtb) to be the infectious agent of tuberculosis in 1882, it has defied efforts by scientists to prevent or cure the disease. The presence of Mtb DNA in ancient Egyptian mummies (dated 1550-1080 BC) suggests a long-standing evolutionary relationship between this bacterium and humans. Despite the world-wide application of BCG vaccination and other anti-Mtb interventions, Mtb remains one of the deadliest human pathogens killing annually two million people. Eight to ten million new cases of active tuberculosis occur each year mainly due to asymptomatic people chronically infected with Mtb. The ability of Mtb to persist in individuals with apparently normal immune systems implies that Mtb has developed strategies to avoid, evade, and even subvert our host defense system. To date, BCG is the only licensed vaccine against tuberculosis (TB). It protects against disseminated forms of TB in children but not against pulmonary TB in adults. However, after 100 years of its discovery, the protective mechanism(s) of BCG is still unknown. Although initially it was thought that adaptive immunity is responsible for this protection, many studies suggested otherwise. We have recently demonstrated that the systemic administration of BCG expands and reprograms stem cells to generate protective innate immunity in pre-clinical mouse models of TB. In the current study, we aim to investigate the potential translation of this approach to humans.