IMR Press / FBL / Volume 8 / Issue 5 / DOI: 10.2741/1004

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Immunological tolerance and its breakdown in Chagas' heart disease: role of parasitokines
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1 Department of Medicine, Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA
2 Department of Parasitology, Institute of Tropical Pathology and Public Health, Universidade Federal de Goias, Caixa Postal 1031, 74001-970 Goiania, Brazil
3 Department of Pathology, Parasitology Research Center, Tufts Medical School, 136 Harrison Avenue, Boston, MA 02111, USA
Front. Biosci. (Landmark Ed) 2003, 8(5), 218–227;
Published: 1 January 2003

Chagas' disease, a debilitating condition inflicting millions of people in Latin America, is caused by infection with the protozoan parasite Trypanosoma cruzi. One characteristic sequel to the subdued acute infection is electocardiographic alterations in about one third of the patients that reach the chronic phase of disease. Another feature of chronic Chagas' disease is the paucity of parasites in the diseased heart. There have been many debates whether chronic chagasic cardiomyopathy (CCC) is a consequence of parasite persistence or autoimmunity, a central question that will clearly influence the strategies for disease prevention and treatment. In this review, we summarize the pros and cons of each side and provide a novel view on the genesis, and hence treatment of, CCC. In particular, we emphasize the contribution of parasite-derived danger signal, such as parasitokines, to the breakdown of self-tolerance in T. cruzi infection. Accordingly, we argue that a more efficient way of countering immune subversion and autoimmune responses induced by the parasite would be targeting key parasitokines rather than blocking parasitic epitopes cross-reactive with host antigens. Finally, based on current knowledge on immune regulation, especially in transplantation models, we propose that future focus of CCC treatment should rely on efforts to restore the immunological tolerance to self-antigens concurrent with regimens to reduce the parasite load as much as possible through immunological and chemotherapy procedures.

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