ANALYSIS OF THE EVENTUAL MODULATORY ROLE OF PD-1/PD-L1 INTERACTION IN THE CHRONIC PHASE OF THE MURINE INFECTION WITH Trypanosoma cruzi

Abstract

Chagas disease, a human disease induced by the flagellate protozoan Trypanosoma cruzi, has no spontaneous cure, progressing to chronicity. In the chronic phase, a significant fraction of patients develop diseases of the heart and/or digestive tract, which appear to be the result of local damage induced by the parasite and immune system. It is unknown the responsible cause for the inefficiency of the immune system in the complete destruction of T. cruzi. One possibility might be immune exhaustion, a negative regulation of effector activity of parasite specific CD4+ and CD8+ cells that prevents them from mediating an efficient effector activity that results in a sterile control the parasite. In this project we intend to verify if in the chronic phase of murine infection by T. cruzi Sylvio X10/4 the PD-1/PD-L1 interaction negatively modulates the activity of effector T lymphocytes. Furthermore, we will examine if the treatment of chronic animals with monoclonal anti-PD-L1 antibodies determines a decrease in parasite load and heart disease.