Karolina Maciag, MD, PhD

Tuberculosis (TB) causes over 1.5 million deaths per year, while lengthy and toxic treatment for TB disease additionally harms millions more. Research efforts to prevent TB disease have not yet yielded an effective vaccine, in part due to our incomplete understanding of the immune response to the TB bacterium. Our research will provide insights into the immune pathways needed for effective TB clearance, so that better vaccines and therapies can be developed. In non-human primates, a species-specific vaccine has been developed that is relatively effective in preventing TB infection. We will integrate analyses and data from lung tissue in mice with that from vaccinated, experimentally infected non-human primates, and from human deceased donors across the spectrum of asymptomatic to active TB lung disease. This cross-species strategy will prioritize lists of candidate genes and pathways to find those most likely to be relevant to immune control of human pulmonary TB.

Update:

Initially, we wanted to identify new ways in which infected macrophages (a type of immune cell) that could be activated by T cells to kill TB bacteria, in addition to using the well-known macrophage-activating signal interferon gamma. Surprisingly, we found that T cells without interferon gamma actually make TB disease worse instead of better. This discovery shows that having a balance between immune pathways that depend on interferon gamma and those that don't is crucial for effective T cell responses against TB.