Cardiac myosin autoimmunity in acute Chagas' heart disease

Infection with Trypanosoma cruzi, the agent of Chagas' disease, may induce antibodies and T cells reactive with self antigens (autoimmunity). Because autoimmunity is generally thought to develop during the chronic phase of in fection, one hypothesis is that autoimmunity develops only after long-term, low-level stimulation of self-reactive cells. However, preliminary reports suggest that autoimmunity may begin during acute T. cruzi infection. The g oal of the present study was to investigate whether cardiac autoimmunity co uld be observed during acute T. cruzi infection. A/J mice infected with the Brazil strain of T. cruzi for 21 days developed severe myocarditis, accomp anied by humoral and cellular autoimmunity. Specifically, T. cruzi infectio n induced immunoglobulin G (IgG) autoantibodies and delayed type hypersensi tivity (DTH) to cardiac myosin. This autoimmunity resembles that which deve lops in A/J mice immunized with myosin in complete Freund's adjuvant in tha t myosin-specific antibodies and DTH responses both develop by 21 days post infection or postimmunization. While the levels of myosin IgG in T. cruzi-i nfected mice were slightly lower than those in myosin-immunized mice, the m agnitude of myosin DTH in the two groups was statistically equivalent. In c ontrast, C57BL/6 mice, which are resistant to myosin-induced myocarditis an d its associated autoimmunity, developed undetectable or low levels of myos in IgG and did not exhibit myosin DTH or myocarditis upon T. cruzi infectio n. Therefore, humoral and cellular cardiac autoimmunity can develop during acute T. cruzi infection in the genetically susceptible host.