Grant: CIHR Fellowship

Almost 37 millions of people are living with HIV (PLWH) worldwide, including 75,000 in Canada. HIV infection is characterized by a progressive destruction of the overall immune defenses. Actual HIV treatments help PLWH to live almost as long as people who are not infected by HIV. However, the virus persists and hides within their body and exhausts their immune system. Recently, a population of human immune cells, called "regulatory T-cells" (Treg) has been identified to contribute in cancer and chronic viral illnesses progression. It has also been demonstrated that the levels of Tregs are higher in PLWH than general population in line with disease progression as these cells are able to inhibit anti-HIV immune responses. Besides Tregs, another type of immune cells, Th17 cells, plays a pivotal role in the maintenance of mucosal immunity and imbalance between Th17 and Tregs results in HIV disease progression. We hypothesize that changes in cellular metabolism contribute in Tregs increased frequencies, which in turn, help HIV to hide in viral reservoirs of PLWH. Specifically, we aim to understand (1) what is the status of Th17/Treg balance in PLWH with different clinical outcomes; (2) what are the metabolic mechanisms involved in Th17/Treg balance during HIV infection; and, (3) how Tregs contribute in HIV persistence and the immuno-deficiency. In this regard, our laboratories will use different well-established experiments on biological specimens from PLWH with different clinical and therapeutic outcomes. This research will help to develop new therapeutic approaches aimed at modulating deleterious functions of Tregs. Targeting of Tregs with appropriate immuno-therapeutic interventions in PLWH, could lead to a better immune recovery and might help to find an HIV cure.