A cardiac myosin-specific autoimmune response is induced by immunization with Trypanosoma cruzi proteins.
Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we investigated whether immunity to T. cruzi antigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasite Leishmania amazonensis did not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induce T. cruzi-specific immunity. These results suggest that immunization with cardiac myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.
Leon
Juan S
JS
Department of Microbiology-Immunology, The Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Daniels
Melvin D
MD
Toriello
Krista M
KM
Wang
Kegiang
K
Engman
David M
DM
D000818:Animals; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases; D015551:Autoimmunity; D024722:Cardiac Myosins / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D006968:Hypersensitivity, Delayed; D007114:Immunization; D007132:Immunoglobulin Isotypes / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015800:Protozoan Proteins / Q000008:administration & dosage* / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D001323:Autoantibodies; D007132:Immunoglobulin Isotypes; D015800:Protozoan Proteins; D024722:Cardiac Myosins