Development and significance of cardiac myosin autoimmunity induced by Trypanosoma cruzi infection in experimental acute Chagas heart disease

Chagas heart disease (CHD) is a dilated cardiomyopathy that develops years after infection with the protozoan Trypanosoma cruzi and is prevalent throughout Central and South America. The observations that CHD patients develop autoimmune responses and cardiac inflammation in the apparent absence of parasites suggested that CHD may be an autoimmune disease. The true mechanisms of cardiac inflammation are unknown. We have investigated cardiac autoimmune responses in an experimental model of CHD. A/J mice infected with the Brazil strain of T. cruzi develop an acute myocarditis associated with cardiac myosin-specific delayed type hypersensitivity (DTH) and production of myosin-specific antibodies. Interestingly, immunization of mice with T. cruzi antigens in CFA also induced myosin-specific DTH and IgG. To address the contribution of myosin autoimmunity to myocarditis, we injected myosin-coupled splenocytes into mice prior to infection and found that, while myosin-specific DTH was decreased, myocarditis was not affected. In contrast, injection of T. cruzi-coupled splenocytes into mice prior to infection increased mortality, increased parasitosis and decreased myocarditis. Lastly, we investigated the use of captopril, an angiotensin converting enzyme inhibitor, for the treatment of experimental CHD and experimental autoimmune myocarditis induced by myosin immunization in A/J mice. We found that captopril reduced the severity of myocarditis in both diseases. In conclusion, these results suggest that infection with T. cruzi can induce rapid myosin-specific autoimmune responses in susceptible mice. The induction of myosin autoimmune responses by T. cruzi infection may be due to myocardial damage or immune responses to cross-reactive T. cruzi antigens. Myosin autoimmunity is not essential to acute myocarditis but anti-T. cruzi responses do participate in cardiac inflammation and control of the parasite. Whether myocarditis is induced by parasite infection or myosin immunization, myocarditis can be effectively treated with captopril.