Grant: Operating Grant

Tuberculosis (TB) is an infectious disease that left untreated leads to life-threatening pathology in the lungs. Globally, the bacteria that causes TB is thought to infect about 2 billion people, with an estimated 9 million of these progressing each year to active TB disease. In Canada, rates are TB are higher in immigrants from high incidence countries, but they are particularly high in Aboriginal people. Indeed,during an outbreak in a village of Nunavik, Quebec, over 5% of the population was diagnosed with active TB in one year and over half of the community was investigated as either a case or a contact of a TB case. In order for the bacteria that causes TB to be such a successful pathogen of humans, it has learned to live with, and indeed, exploit our immune system, to its benefit. One of the ways this bacteria does this is by activating a human immune recognition molecule, called NOD2. Previous work by the applicant has shown that NOD2 is critical for our ability to fight this pathogen, in part because NOD2 is exquisitely sensitive for the detection of these particular bacteria. Yet a number of key questions remain unanswered and are the subject of this proposal. In the investigations proposed, we aim to determine how NOD2 recognizes mycobacteria at three levels: the protein, the cell and the lungs. By understanding the importance of NOD2 for the immune response to TB, we shall gather information that can guide the generation of new vaccines against this ancient disease.