Autoimmunity in Chagas' heart disease

Abstract

The time scale dissociation between high parasitemia and tissue pathology, allied to the absence of parasites in the heart lesions of chronic Chagas' disease cardiopathy, casted doubt on the direct participation of Trypanosoma cruzi in tissue lesions. Moreover, the heart tissue lesions in chronic Chagas' disease cardiopathy are associated to an inflammatory mononuclear cell infiltrate, presumably the ultimate effectors of tissue damage. It has been hypothesized that the inflammatory cell infiltrate could mediate a delayed hypersensitivity process directed to the heart tissue components, an autoimmune response triggered by immunological cross-reactivity in the course of a protective immune response against some T.cruzi antigen homologous to heart proteins. However, little is known about the efector role of the T cells in the infiltrate, or about the nature of the antigen that lead to their accumulation in tissue. In this paper, we will review the published evidence on autoimmunity and immunological cross-reactivity between T. cruzi and the mammalian host, along with data generated in our laboratory. The definition of the precise role played by autoimmunity in the pathogenesis of Chagas' disease cardiopathy may have important consequences both for immunoprophylaxis and for the therapeutic approach of chronic Chagas' disease.

Chagas' heart disease

“…In addition, molecular biology techniques now permit the detection of circulating T. cruzi antigens in a much larger contingent of chagasic patients in whom the conventional serologic methods fail for such purpose 117,118 . It is plausible to speculate that even low-grade persistent parasitism may lead to a continuous antigenic feedback loop to the autoimmune system, which may constitute the main damaging mechanism in the late phase [119][120][121] .…”

“…Moreover, specific epitopes associated with the host immune response and potentially able to produce myocardial damage have been recently identified 120,[154][155][156][157][158][159][160][161][162] . There is also evidence that persistent T. cruzi antigen presentation to macrophages could lead to cytokyne production, thus modulating the immune response and possibly causing the relative immunosuppressive state responsible for perpetuation of infection 121,163,164 .…”

Analysis of the Presence of Trypanosoma Cruzi in the Heart Tissue of Three Patients With Chronic Chagas’ Heart Disease

“…Parasitic DNA and human genomic DNA are easily distinguishable because T. cruzi minicircle kDNA is characterized by an unequal A:C:G:T ratio, with less than 10% of the nucleotides being C. 2 The scarcity of the parasite in the chronic phase suggests that autoimmune processes are involved in the pathology of Chagas' disease. 5,6 An autoimmune response may be initiated by T cells that are activated by T. cruzi antigens that closely resemble self-antigens. 7 Alternatively, the parasite may cause tissue damage that leads to the exposition of cryptic host antigens and subsequently to the induction of the inflammation.…”

Immunohistochemical studies in acute and chronic canine chagasic cardiomyopathy

“…The mechanisms involved in the genesis of chronic chagasic myocarditis are very controversial, and inflammatory infiltrate has a crucial role in the induction of congestive cardiac insufficiency in chronic Chagas' disease [4]. The presence of a predominantly chronic lymphocyte infiltrate in the absence or scarcity of parasites has suggested the involvement of immune mechanisms [9,10]. These mechanisms can be important in the emergence of lesions in the myocardiocytes and in exacerbation of the inflammatory process.…”