The fundamental question that drives the research in my laboratory is how the immune response is regulated so that an invading pathogen is eliminated or controlled with minimal collateral damage to the host. A protective immune response is required in order to survive infection by a microorganism, such as parasites, bacteria or viruses. If the immune response is too weak then the pathogen will win, while an immune response that is too strong can cause collateral damage, called immune-mediated pathology and disease. My laboratory asks what is important for balancing a protective immune response and preventing immune-mediated pathology during chronic infection. My research focuses on an essential immune cell, the T regulatory cell (Tregs) that regulates the amount of immune response directed at invading microorganisms. In addition to preventing unwanted immune responses directed at the body’s own tissues, Tregs play an important role in tuning the immune response to infection. If there is an impairment of Treg development or function then uncontrolled inflammation, immune-mediated pathology, and disease can occur. We use the parasite Toxoplasma gondii to investigate how immune regulation is altered by chronic infection. Ingestion of T. gondii results in a chronic infection with tissue cysts residing in skeletal muscle and the central nervous system.
My laboratory uses a mouse model of Toxoplasma infection to study how the establishment of infection and its chronicity alter Treg and their responses. We showed that in mice, T. gondii infection causes severe inflammation of the muscle (myositis) and a loss of muscle function. We found that this happens because the infection alters the function of Tregs and they acquire a tissue injurious function, instead of a tissue reparative function. We further showed that chronic infection stunts the ability of macrophages to participate in the wound healing response. Finally, we found that chronic infection impairs the renewal of muscle stem cells that are required for the regeneration of skeletal muscle. We are currently asking questions about how the interactions between these 3 critical cell types occur, and how chronic infection impacts this cellular network. We are also interested in identifying methods to intervene and dampen inflammation and promote the return of function to the muscle.