Current concepts in immunoregulation and pathology of human Chagas disease

Abstract

Purpose of review-Chagas disease is a complex ailment caused by infection with Trypanosoma cruzi. It afflicts millions in Latin America. Years of studies have focused on the development of pathology in Chagas disease and recent studies have helped us understand the cellular mechanisms behind differential clinical evolution of Chagas disease.Recent findings-We discuss recent findings concerning the cellular immune response in human Chagas disease focusing on immunoregulation and the development of pathology. We seek to put several findings into the context of a disease that initially controls an extreme and patent infection, and later progresses to a chronic phase marked by the presence (cardiac and digestive forms), or not (indeterminate form), of associated pathology.Summary-Several theories exist to explain differential clinical evolution of Chagas disease. A coherent understanding of these theories will certainly aid in determining what combination of them approximates the true development of chagasic pathology. For achieving the goal of developing a successful therapy or intervention, it is critical that no theory be excluded at this point, but. Rather, rather that a thoughtful analysis and assimilation of the best components of each system into a central theory that best fits the reality of human Chagas disease is desirable.

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

“…In contrast, a wellexecuted immune response, capable of reducing parasite burden and limiting its inflammatory consequences, results in less tissue damage. Some in-depth overviews of the immunoregulation and pathology of the heart in Chagas disease have been published during the current decade (Higuchi et al 2003, Tarleton 2003a, b, MarinNeto et al 2007, Dutra & Gollob 2008.…”

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

“…It is well accepted that the host's immune response plays a key role during Trypanosoma cruzi infection, leading to either parasite control during the acute phase or to participation in the pathology development during the chronic phase (Dutra & Gollob 2008). Antibody production and T-cell responses have been studied in patients with Chagas disease (Morgan et al 1996, Cordeiro et al 2001) and experimental models (Giordanengo et al 2000, Guedes et al 2008.…”

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] .…”