Lorissa Smulan, PhD

Tuberculosis (TB) is caused by  infection with the bacterium Mycobacterium tuberculosis (Mtb). TB is the leading cause of death worldwide. Treatment of TB is complicated due to the requirement of multiple drugs and length of treatment. It is important to identify immune factors contributing to disease progression for future development of therapies to treat TB. Progression of TB is strongly associated with increased levels of type I interferons, a family of proteins that play important roles in inflammation. 

Sirtuin 3, a protein that is important for metabolism, is decreased in immune cells infected with Mtb. We have identified a novel link between sirtuin 3 and type I interferon production. We will investigate how sirtuin 3 modulates type I interferon production. We propose that increasing sirtuin 3 activity will prevent production of type I interferons during infection and identify sirtuin 3 as an attractive target for “host-directed therapies” for treatment of TB. This therapy does not fight TB itself, but targets proteins it needs to live and multiply.

Update:

Mitochondria are like power plants inside cells and are crucial in how our bodies respond to infections like tuberculosis (TB). When mitochondria are damaged during infection with Mycobacterium tuberculosis, the pathogen causing TB, they release signals that trigger inflammation, which worsens the disease. Sirtuins are important proteins that help regulate how mitochondria work and handle stress caused by infections. When cells are infected with M. tuberculosis, sirtuin activity goes down. We have found that when sirtuin activity is reduced by infection, mitochondrial function is disrupted. When we activated sirtuins in mitochondria during M. tuberculosis infection, mitochondrial function was restored. This suggests that boosting sirtuin activity in mitochondria could be a way to fight TB more effectively. We will continue to explore how sirtuins in mitochondria affect their function and the immune response during TB infection.