The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

Abstract

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.

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

“…Although often they are not associated with amastigote nests or trypomastigotes, T. cruzi antigens may be present (Higuchi 1995, Reis et al 1997). CD4 + T cells, though less prominent in the chronic stage, are suggested to be associated with myocyte death and increased animal mortality (Soares et al 2001) and appear to represent an autoreactive phenotype that contributes to tissue destruction (Soares and Santos 1999). At this later stage, continued production of IFN-γ and IL-2 is believed to stimulate lytic antibody production by B cells (Brener and Gazzinelli 1997).…”

Importance of CD8 T cell-mediated immune response during intracellular parasitic infections and its implications for the development of effective vaccines

“…cruzi is a parasite that persists for long periods of time causing a chronic inflammatory disease. Under certain circumstances T cells exacerbate the immune response causing an increase in tissue pathology or autoimmunity (Soares et al 2001a). However, this autoimmune response has been associated with CD4 Th1 cells (dos Santos et al 1992, Soares et al 2001b).…”

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana

“…The actual finding of the parasite at this late stage of the disease is infrequent, although the use of highly sensitive techniques allows the recognition of parts of the parasite in the myocardium 7 . This finding and others suggest that an autoimmune process plays a major role in the chronic phase of the disease 8,9 .…”