Mechanisms of pathogenesis in Chagas disease

Abstract

Chagas disease, caused by the obligate unicellular parasite Trypanosoma cruzi, presents itself in a diverse collection of clinical manifestations, ranging from severe, fatal heart and digestive tract pathologies to unapparent or minor alterations that do not compromise survival. Over the years, a number of mechanisms have been proposed to explain the pathogenesis of chagasic tissue lesions, all of which have faced some criticism or been received with skepticism. This article excludes the autoimmunity hypothesis for Chagas disease because it has been extensively reviewed elsewhere, and summarizes the various alternative hypotheses that have been advanced over the years. For each of these hypotheses, an outline of its main tenets and key findings that support them is presented. This is followed by the results and comments that have challenged them and the caveats that stand on their way to wider acceptance. It is hoped that this writing will draw attention to our shortcomings in understanding the pathogenesis of Chagas disease, which, unfortunately, continues to figure among the most serious health problems of the American continent.

Humoral Immune Response against P2β from Trypanosoma cruzi in Persons with Chronic Chagas Disease: Its Relationship with Treatment Against Parasites and Myocardial Damage

“…Several lines of evidence implicate that parasite strains and persistence, genetic and nutritional features of patients, and the quality of the immune response are involved in the establishment of CCC. [31][32][33] Results of our longitudinal study do not lend support to the assessment of antibodies to P2β as a surrogate marker of progression from indeterminate disease to heart disease. However, a slight but statistically significant trend to increased antibody reactivity to P2β was seen in patients with evolving CCC.…”

I Diretriz Latino-Americana para o Diagnóstico e Tratamento da Cardiopatia Chagásica

“…It is not clear whether the autoimmunity-dependent injury to cardiac structures is decisive for the installation of the characteristic lesions of CCC. Despite the current knowledge limitation, the theory that the immune system reaction to T. cruzi infection is actually a "two-edged sword" and plays as fundamental role in the chronic phase of chagasic myocarditis is supported by an extensive body of experimental and clinical evidence [24][25][26][27][39][40][41] .…”

“…It has been postulated that the balance and relative pathological stability of that the indeterminate form, in which the immune mechanism should be essentially modulated in the protective direction, are disrupted by still obscure factors, when inflammation, necrosis and fibrosis become more intense, diffuse and progressive [24][25][26][27]39,41 . Several factors can determine the stability or instability of the process: parasite load, parasite strain or tissue tropism, duration of infection, and genetic components of the host.…”

“…Several mechanisms contribute to the pathogenesis of the cardiac lesions and consequent installation of the pathophysiological disorders, according to recent reviews [24][25][26][27][28] .…”

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

“…Although the responsible mechanisms are yet to be determined, Chagas heart disease appears to evolve from localized myocardial damage to a clinical form of congestive cardiomyopathy with extensive myocardial damage 10,13,39 . A cardiac autoimmune response, aimed at the cardiac muscarinic receptors, and several other hypotheses have been postulated in order to explain the progression of myocardial damage 4,28,29,33,34,36 .…”