Research Summary

Research in the Tarleton laboratory focuses on the immunology and pathogenesis of Trypanosoma cruzi infection and the resulting disease syndrome known as Chagas disease. T. cruzi is a protozoan parasite that infects approximately 18 million people in Latin America with 90 million more at risk of infection. Chagas disease is the single most common cause of congestive heart failure and sudden death in the world and the leading cause of death among young-to-middle-age adults in endemic areas of South America . There are no vaccines for prevention of T. cruzi infection and current chemotherapeutic regimens are of limited efficacy.

T. cruzi is a blood-borne parasite with an extracellular non-replicative trypomastigote stage that circulates throughout the body and an obligate intracellular stage capable of replication within a variety of types of host cells. Soon after invasion of host cells, the trypomastigotes move from the phagolysosome into the host cell cytoplasm during their differentiation into amastigote forms. Within the host cell, the amastigotes undergo a series of divisions resulting in the production of 500 or more progeny from a single invading parasite over the span of 4-5 days. Amastigotes then convert back into trypomastigotes and are released from the host cell, resulting in that cell's destruction, and repeat the cycle of invasion, replication and release. Although the host immune response generally limits the parasite load, there is scant evidence that humans or other mammals can completely clear the infection.

Three broad questions are being addressed by the research in the Tarleton lab: 1) How is immune control initiated and maintained during the infection, 2) How does T. cruzi manage to avoid immune clearance and maintain an infection for decades in hosts, and 3) What is the relationship between immunity, parasite persistence, and disease development? The ultimate goals of these investigations are to provide insights into the immunologic basis of parasite control and pathogenesis in T. cruzi infection and to use this information to design methods for prevention of infection or intervention in chronic disease.