The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet.
Chagas' disease is a major health problem in Latin America, where it constitutes one of the leading causes of heart failure. About one fourth of Trypanosoma cruzi-infected individuals develop chronic chagasic cardiomyopathy (CChC), the most severe form of the disease. CChC is histologically characterized by the presence of multifocal inflammatory infiltrates in the heart, composed mainly by mononuclear cells, usually adhered to myocytes and leading to myocytolysis, and frequently by interstitial fibrosis. The pathogenesis of CChC is still unclear, despite intense investigations both in human beings and in animal models of the disease. Although tissue parasitism is rare in the chronic phase of infection, an immune response targeted to persistent parasites or parasite antigens is suggested, by some authors, as the pathogenic mechanism of CChC. Other researchers affirm that the lack of correlation between tissue parasitism and intensity of inflammation suggests, along with the presence of autoreactive immune responses, that CChC results from the action of an autoimmune response. Herein we review reports from the literature and our own data, which together indicate, on one hand, the participation of parasite-specific immune responses and, on the other hand, clearly demonstrate the participation of heart-specific immune responses in the pathogenesis of CChC. Moreover, multiple factors may determine whether an individual in the indeterminate form of the disease will develop CChC. The mechanisms by which T. cruzi breaks immunological tolerance to heart antigens are also discussed.
Soares
M B
MB
Laboratório de Imunofarmacologia, Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil.
Pontes-De-Carvalho
L
L
Ribeiro-Dos-Santos
R
R
D000818:Animals; D015551:Autoimmunity; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000276:immunology*