Induction of cardiac autoimmunity in Chagas heart disease: A case for molecular mimicry

Cunha-Neto, Edécio; Bilate, Angelina M.; Hyland, Kenneth V.; Fonseca, Simone Gonçalves; Kalil, Jorge; Engman, David M.

doi:10.1080/08916930500485002

Cited by 121 publications

(96 citation statements)

References 182 publications

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“…However, in order to definitively "prove" molecular mimicry occurs, it must be demonstrated that a single antigen receptor (T cell or antibody) reacts with epitopes of both the parasite and the host and can promote tissue inflammation. The first element crossreactivity of a T cell clone with parasite and host peptides has been demonstrated, but the second has not [54,58].…”

Section: Parasite-induced Autoimmunitymentioning

confidence: 99%

Chagas Heart Disease Pathogenesis: One Mechanism or Many?

Bonney

Engman²

2008

CMM

151

144

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Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, is the leading cause of infectious myocarditis in the world. The etiology of CHD is unclear and multiple mechanisms have been proposed to explain the pathogenesis of the disease. This review describes the proposed mechanisms of CHD pathogenesis and evaluates the historical significance and evidence supporting each. Although the majority of CHD-related pathologies are currently attributed to parasite persistence in the myocardium and autoimmunity, there is strong evidence that CHD develops as a result of additive and even synergistic effects of several distinct mechanisms rather than one factor.

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Section: Parasite-induced Autoimmunitymentioning

confidence: 99%

Chagas Heart Disease Pathogenesis: One Mechanism or Many?

Bonney

Engman²

2008

CMM

151

144

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“…One of the most accepted explanations claims that chronic cytokine production in the heart is responsible for most of the observed cardiac alterations. 2,11 Clinical studies and animal models have shown that right and left ventricles are compromised during the time course of Chagas disease. 3,[8][9][10][12][13][14][15] It is already known that right ventricle function is dysregulated during Chagas disease, however, few studies have pointed out which molecular mechanisms are responsible for right ventricular myocyte dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Altered Cardiomyocyte Function and Trypanosoma cruzi Persistence in Chagas Disease

Cruz¹,

Santos‐Miranda²,

Sales-Junior³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Chagas disease, caused by the triatominae Trypanosoma cruzi, is one of the leading causes of heart malfunctioning in Latin America. The cardiac phenotype is observed in 20-30% of infected people 10-40 years after their primary infection. The cardiac complications during Chagas disease range from cardiac arrhythmias to heart failure, with important involvement of the right ventricle. Interestingly, no studies have evaluated the electrical properties of right ventricle myocytes during Chagas disease and correlated them to parasite persistence. Taking advantage of a murine model of Chagas disease, we studied the histological and electrical properties of right ventricle in acute (30 days postinfection [dpi]) and chronic phases (90 dpi) of infected mice with the Colombian strain of T. cruzi and their correlation to parasite persistence. We observed an increase in collagen deposition and inflammatory infiltrate at both 30 and 90 dpi. Furthermore, using reverse transcriptase polymerase chain reaction, we detected parasites at 90 dpi in right and left ventricles. In addition, we observed action potential prolongation and reduced transient outward K + current and L-type Ca 2+ current at 30 and 90 dpi. Taking together, our results demonstrate that T. cruzi infection leads to important modifications in electrical properties associated with inflammatory infiltrate and parasite persistence in mice right ventricle, suggesting a causal role between inflammation, parasite persistence, and altered cardiomyocyte function in Chagas disease. Thus, arrhythmias observed in Chagas disease may be partially related to altered electrical function in right ventricle.

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“…This hypothesis is based on the apparent absence of parasites in cardiac inflammatory lesions and the presence of anti-self immune responses in chronic Chagas cardiomyopathy patients, caused by either autoantibodies or autoreactive T cells, derived by molecular mimicry between parasite and host antigens , Girones et al 2005. This supposition suggested that etiologic treatment would be of little benefit (Cunha-Neto et al 2006).…”

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confidence: 99%