Trypanosoma cruzi alters adherens junctions in cardiomyocytes

Melo, Tatiana G.; Meirelles, Maria de Nazareth Leal de; Pereira, Mirian Cláudia de Souza

doi:10.1016/j.micinf.2008.07.044

Cited by 12 publications

(11 citation statements)

References 18 publications

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“…Several molecules at the cardiomyocyte surface, including carbohydrates, fibronectin, and heparan sulfate proteoglycans, are involved in the parasite-host cell recognition and mediate the invasion process (3,4,7,8,45). Structural changes in cardiomyocytes observed during intracel-lular development of the parasite may contribute to a reduction of transmission of the contractile force and lead to alterations in function of the heart in Chagas' disease (1,37,38,39,46). Finally, T. cruzi-infected cardiomyocytes elicit a strong immune response, characterized by the production of the chemokines RANTES and macrophage inflammatory protein 2 and the cytokines gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣), which triggers a potent nitric oxide-dependent trypanocidal activity (33).…”

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confidence: 99%

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

et al. 2011

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Chagas' disease, caused by the hemoflagellate protozoan Trypanosoma cruzi, affects millions of people in South and Central America. Chronic chagasic cardiomyopathy, the most devastating manifestation of this disease, occurs in approximately one-third of infected individuals. Events associated with the parasite's tropism for and invasion of cardiomyocytes have been the focus of intense investigation in recent years. In the present study, we use murine microarrays to investigate the cellular response caused by invasion of primary murine cardiomyocytes by T. cruzi trypomastigotes. These studies identified 353 murine genes that were differentially expressed during the early stages of invasion and infection of these cells. Genes associated with the immune response, inflammation, cytoskeleton organization, cell-cell and cell-matrix interactions, apoptosis, cell cycle, and oxidative stress are among those affected during the infection. Our data indicate that T. cruzi induces broad modulations of the host cell machinery in ways that provide insight into how the parasite survives, replicates, and persists in the infected host and ultimately defines the clinical outcome of the infection.

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confidence: 99%

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

et al. 2011

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“…In addition to disruption of the cytoskeletal architecture by the parasite, cell–cell adhesion (adherens junctions) and intercellular communication (gap junctions), which play important physiological roles in cardiac tissue, are also been disrupted by T. cruzi infection (Adesse et al, 2008, 2011b; Melo et al, 2008). Alteration in spatial distribution and down-regulation of the adherence junction proteins N-cadherin and β-catenin in T. cruzi -infected cardiomyocytes (Melo et al, 2008) may interfere with tissue integrity and perturb the function of the cardiac conduction system, as has been proposed to be the case in arrhythmogenic cardiomyopathies (Mezzano and Sheikh, 2012).…”

Section: Effect Of T Cruzi Infection In Cardiomyocyte Physiologymentioning

confidence: 99%

“…Alteration in spatial distribution and down-regulation of the adherence junction proteins N-cadherin and β-catenin in T. cruzi -infected cardiomyocytes (Melo et al, 2008) may interfere with tissue integrity and perturb the function of the cardiac conduction system, as has been proposed to be the case in arrhythmogenic cardiomyopathies (Mezzano and Sheikh, 2012). Additionally, electrical conduction disturbance, frequently seen in both acute and chronic phases of Chagas diseases, seems to be related to altered gap junction (connexin-43) coupling of cardiomyocytes induced by T. cruzi (de Carvalho et al, 1992, 1994; Adesse et al, 2008, 2011b).…”

Section: Effect Of T Cruzi Infection In Cardiomyocyte Physiologymentioning

confidence: 99%

Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction

Calvet¹,

Melo²,

Garzoni³

et al. 2012

Front. Immun.

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Trypanosoma cruzi, the etiological agent of Chagas disease, exhibits multiple strategies to ensure its establishment and persistence in the host. Although this parasite has the ability to infect different organs, heart impairment is the most frequent clinical manifestation of the disease. Advances in knowledge of T. cruzi–cardiomyocyte interactions have contributed to a better understanding of the biological events involved in the pathogenesis of Chagas disease. This brief review focuses on the current understanding of molecules involved in T. cruzi–cardiomyocyte recognition, the mechanism of invasion, and on the effect of intracellular development of T. cruzi on the structural organization and molecular response of the target cell.

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“…Primary cultures of murine cardiac myocytes have been the method of choice to demonstrate alterations in the host cell induced by this parasite. In these studies, many as-pects of this relationship were clarified, such as alterations in intracellular calcium dynamics (2,17), changes in the cell cytoskeleton (24,30), and cell-cell junction (1,12). Gap junction channels are critical to maintaining cardiac homeostasis by allowing the free flow of ions and metabolites between cardiac myocytes, which contributes to the synchronized contraction of and signal exchange throughout the tissue.…”

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Amiodarone Inhibits Trypanosoma cruzi Infection and Promotes Cardiac Cell Recovery with Gap Junction and Cytoskeleton Reassembly In Vitro

Adesse

Azzam

Meirelles

et al. 2011

Antimicrob Agents Chemother

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We present the results of the first detailed study of the antiproliferative and ultrastructural effects of amiodarone on Trypanosoma cruzi, the causative agent of Chagas' disease. Moreover, we report the effects of this compound on the recovery of F-actin fibrils, connexin43, and contractility in T. cruzi-infected cardiac myocytes. Amiodarone is the most prescribed class III antiarrhythmic agent and is frequently used for the symptomatic treatment of Chagas' disease patients with cardiac compromise. In addition, recent studies identified its antifungal and antiprotozoal activities, which take place through Ca 2؉ homeostasis disruption and ergosterol biosynthesis blockade. We tested different concentrations of amiodarone (2.5 to 10 M) on infected primary cultures of heart muscle cells and observed a dose-and time-dependent effect on growth of the clinically relevant intracellular amastigote form of T. cruzi. Ultrastructural analyses revealed that amiodarone had a profound effect on intracellular amastigotes, including mitochondrial swelling and disorganization of reservosomes and the kinetoplast and a blockade of amastigote-trypomastigote differentiation. Amiodarone showed no toxic effects on host cells, which recovered their F-actin fibrillar organization, connexin43 distribution, and spontaneous contractility concomitant with the drug-induced eradication of the intracellular parasites. Amiodarone is, therefore, a promising compound for the development of new drugs against T. cruzi.

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Trypanosoma cruzi alters adherens junctions in cardiomyocytes

Cited by 12 publications

References 18 publications

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

Trypanosoma cruzi Infection Induces a Global Host Cell Response in Cardiomyocytes

Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction

Amiodarone Inhibits Trypanosoma cruzi Infection and Promotes Cardiac Cell Recovery with Gap Junction and Cytoskeleton Reassembly In Vitro

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