Fas/Fas-L expression, apoptosis and low proliferative response are associated with heart failure in patients with chronic Chagas' disease

Abstract

Chagas' disease affects 16–18 million patients in South America and heart involvement is the major cause of morbidity and mortality. Heart failure is the most severe clinical manifestation of the chronic phase of infection with Trypanosoma cruzi. The intensity and nature of the immune response is associated with the clinical outcome of the disease. In murine models, a low proliferative response and T-cell apoptosis have been observed during acute infection. In the present study the immune response of patients in the chronic phase of infection was analyzed. Patients were divided into: (a) asymptomatic, i.e., without involvement of the heart or digestive system; and (b) with heart failure. Patients with heart failure presented a significantly lower peripheral blood mononuclear cell (PBMC) proliferative response to T. cruzi antigens compared to asymptomatic patients. This low response was associated with antigen-induced apoptosis. Apoptosis of PBMC and a low proliferative response were also associated with double Fas/Fas-L expression and high production of TNF-α, a cytokine known to induce programmed cell death. These results suggest that apoptosis of PBMC, probably triggered by double expression of Fas/Fas-L and TNF-α, is implicated in the immune regulatory mechanism during the chronic phase of Chagas' disease.