Myosin autoimmunity is not essential for cardiac inflammation in acute Chagas' disease.
Infection with the protozoan parasite Trypanosoma cruzi leads to acute myocarditis that is accompanied by autoimmunity to cardiac myosin in susceptible strains of mice. It has been difficult to determine the contribution of autoimmunity to tissue inflammation, because other inflammatory mechanisms, such as parasite-mediated myocytolysis and parasite-specific immunity, are coincident during active infection. To begin to investigate the contribution of myosin autoimmunity to myocarditis, we selectively inhibited myosin autoimmunity by restoring myosin tolerance via injection of myosin-coupled splenocytes. This tolerization regimen suppressed the strong myosin-specific delayed-type hypersensitivity (DTH) that normally develops in infected mice, although it did not affect myosin-specific Ab production. Suppression of myosin autoimmunity had no effect on myocarditis or cardiac parasitosis. In contrast, myosin tolerization completely abrogated myocarditis in mice immunized with purified myosin, which normally causes severe autoimmune myocarditis. In this case, myosin-specific DTH and Ab production were significantly reduced. We also examined the contribution of T. cruzi-specific immunity to inflammation by injection of T. cruzi-coupled splenocytes before infection. This treatment reduced T. cruzi DTH, although there was no effect on parasite-specific Ab production. Interestingly, cardiac inflammation was decreased, cardiac parasitosis was significantly increased, and mortality occurred earlier in the parasite-tolerized animals. These results indicate that myosin-specific autoimmunity, while a potentially important inflammatory mechanism in acute and chronic T. cruzi infection, is not essential for inflammation in acute disease. They also confirm previous studies showing that parasite-specific cell-mediated immunity is important for myocarditis and survival of T. cruzi infection.
Leon
Juan S
JS
Department of Microbiology, The Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Wang
Kegiang
K
Engman
David M
DM
D000208:Acute Disease; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D001324:Autoantigens / Q000276:immunology* / Q000302:isolation & purification; D001327:Autoimmune Diseases / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D024722:Cardiac Myosins / Q000276:immunology* / Q000302:isolation & purification; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D007108:Immune Tolerance; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009205:Myocarditis / Q000276:immunology* / Q000401:mortality / Q000469:parasitology / Q000473:pathology*; D018995:Myosin Heavy Chains / Q000276:immunology / Q000302:isolation & purification; D014349:Trypanosoma cruzi / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001324:Autoantigens; D000939:Epitopes; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains