Trypanosoma cruzi–cardiomyocyte interaction: role of fibronectin in the recognition process and extracellular matrix expression in vitro and in vivo

Calvet, Cláudia M.; Meuser, M. B.; Almeida, de; Meirelles, M. N. L.; Pereira, Mirian Cláudia de Souza

doi:10.1016/j.exppara.2004.04.003

Cited by 37 publications

(24 citation statements)

References 45 publications

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“…In addition to the findings that treatment of either mouse peritoneal macrophages or blood trypomastigotes with human plasma FN increased parasite internalization (40), there are reports that nonphagocytic cells, such as cardiomyocytes and fibroblasts, have their association with TCT augmented by FN (7,41). Based on these observations, it has been suggested that FN bridges parasite-target cell association, leading to enhanced infection.…”

Section: Discussionmentioning

confidence: 96%

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

et al. 2014

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Trypanosoma cruzi, the agent of Chagas disease, binds to diverse extracellular matrix proteins. Such an ability prevails in the parasite forms that circulate in the bloodstream and contributes to host cell invasion. Whether this also applies to the insectstage metacyclic trypomastigotes, the developmental forms that initiate infection in the mammalian host, is not clear. Using T. cruzi CL strain metacyclic forms, we investigated whether fibronectin bound to the parasites and affected target cell invasion. Fibronectin present in cell culture medium bound to metacyclic forms and was digested by cruzipain, the major T. cruzi cysteine proteinase. G strain, with negligible cruzipain activity, displayed a minimal fibronectin-degrading effect. Binding to fibronectin was mediated by gp82, the metacyclic stage-specific surface molecule implicated in parasite internalization. When exogenous fibronectin was present at concentrations higher than cruzipain can properly digest, or fibronectin expression was stimulated by treatment of epithelial HeLa cells with transforming growth factor beta, the parasite invasion was reduced. Treatment of HeLa cells with purified recombinant cruzipain increased parasite internalization, whereas the treatment of parasites with cysteine proteinase inhibitor had the opposite effect. Metacyclic trypomastigote entry into HeLa cells was not affected by anti-␤1 integrin antibody but was inhibited by anti-fibronectin antibody. Overall, our results have indicated that the cysteine proteinase of T. cruzi metacyclic forms, through its fibronectin-degrading activity, is implicated in host cell invasion. E xtracellular matrix (ECM) proteins, which serve as substrates for diverse adhesion molecules and are involved in many important physiological processes, also may mediate cell attachment and/or invasion of pathogenic microorganisms. Among these molecules, fibronectin (FN) has been reported to play a role in adherence to and invasion of host cells by bacteria such as Staphylococcus aureus, Streptococcus pyogenes, and Campylobacter jejuni (1-6). The interaction of fibronectin with Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, also has been described. T. cruzi infection is initiated by metacyclic trypomastigote (MT) from the insect vector. This parasite form is responsible for the initial T. cruzi-host cell interaction upon entering the mammalian host through the skin or by the oral route. Following MT internalization in a membrane-bound vacuole and escape to the cytoplasm, the parasite differentiates into amastigote form. After several rounds of replication, amastigotes transform into trypomastigotes that are released in the circulation upon host cell rupture. Experiments with tissue culture trypomastigote (TCT), which corresponds to the bloodstream trypomastigote, revealed the involvement of fibronectin in target cell adhesion/invasion. The treatment of 3T3 fibroblasts or rat peritoneal macrophages, or TCT, with human plasma FN increased parasite-cell association (7), and binding ...

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Section: Discussionmentioning

confidence: 96%

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

et al. 2014

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“…Our studies showed for the first time that it was possible to discriminate between experimental models of chronic T. cruzi infection having intense (C3H/He) and slight (C57BL/6) FN deposition, which paralleled the degree of heart inflammation and therefore resembled CD patients (Higuchi et al 1987). Although FN expression was down regulated in T. cruzi -bearing cardiomyocytes in vitro (Calvet et al 2004), the presence of the parasite and its antigens triggered the production of FN in skeletal muscle cells (Pinho et al 2002, Marino et al 2003). In benznidazole-treated mice, reduced heart parasitism is accompanied by decreased FN deposition and fibrosis (Andrade et al 1991), supporting a parallelism between heart parasitism and FN expression.…”

Section: Discussionmentioning

confidence: 99%

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Pereira

Vilar-Pereira

Silva

et al. 2014

Mem. Inst. Oswaldo Cruz

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Heart tissue inflammation, progressive fibrosis and electrocardiographic alterations occur in approximately 30% of patients infected by Trypanosoma cruzi, 10-30 years after infection. Further, plasma levels of tumour necrosis factor (TNF) and nitric oxide (NO) are associated with the degree of heart dysfunction in chronic chagasic cardiomyopathy (CCC). Thus, our aim was to establish experimental models that mimic a range of parasitological, pathological and cardiac alterations described in patients with chronic Chagas’ heart disease and evaluate whether heart disease severity was associated with increased TNF and NO levels in the serum. Our results show that C3H/He mice chronically infected with the Colombian T. cruzi strain have more severe cardiac parasitism and inflammation than C57BL/6 mice. In addition, connexin 43 disorganisation and fibronectin deposition in the heart tissue, increased levels of creatine kinase cardiac MB isoenzyme activity in the serum and more severe electrical abnormalities were observed in T. cruzi-infected C3H/He mice compared to C57BL/6 mice. Therefore, T. cruzi-infected C3H/He and C57BL/6 mice represent severe and mild models of CCC, respectively. Moreover, the CCC severity paralleled the TNF and NO levels in the serum. Therefore, these models are appropriate for studying the pathophysiology and biomarkers of CCC progression, as well as for testing therapeutic agents for patients with Chagas’ heart disease.

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“…Fibronectin, a high molecular weight glycoprotein present at the host cell surface, is recognized by fibronectin receptors of the parasite (Ouaissi et al, 1984), which interact with the RGDS (Arg-Gly-Asp-Ser) sequence of fibronectin and mediate parasite entry (Calvet et al, 2004). Immunization with RGDS peptide induced protection in an experimental murine model of acute T. cruzi infection (Ouaissi et al, 1986).…”

Section: Cell Recognition and Invasion Processmentioning

confidence: 99%

“…In experimental systems, ECM accumulation begins during the late acute phase of infection (Andrade et al, 1989; Calvet et al, 2004), concomitantly with the onset of inflammatory infiltrates, indicating that the process of fibrogenesis is triggered in the early stages of T. cruzi infection. A general increase in ECM transcripts and expression was detected by microarray analysis in acute infection (Garg et al, 2003).…”

Section: Effect Of T Cruzi Infection In Cardiomyocyte Physiologymentioning

confidence: 99%

“…Surprisingly, reduction of ECM in T. cruzi -infected cardiomyocytes was detected by silver staining in acute infection in mice (Factor et al, 1993). Additionally, T. cruzi -mediated down-regulated ECM gene expression in cardiomyocyte cultures (Goldenberg et al, 2009; Manque et al, 2011) and a reduction in the synthesis and spatial distribution of fibronectin were detected in heavily infected cardiomyocytes (Calvet et al, 2004; Figure 2 ) even after TGF-β stimulation (Calvet et al, 2009), suggesting that despite the general enhancement of ECM in the heart, the cells harboring the parasites display low ECM expression. The anti-fibrogenic effect of T. cruzi has also been seen in human dermal fibroblasts, with repression of transcription factors that regulate expression of fibroblast genes involved in wound repair and tissue remodeling, including ctgf/ccn2 connective tissue growth factor gene, followed by down-regulation of ECM proteins such as fibronectin and collagen I, suggesting another route of parasite dissemination and infection (Unnikrishnan and Burleigh, 2004; Mott et al, 2011).…”

Section: Effect Of T Cruzi Infection In Cardiomyocyte Physiologymentioning

confidence: 99%

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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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Trypanosoma cruzi–cardiomyocyte interaction: role of fibronectin in the recognition process and extracellular matrix expression in vitro and in vivo

Cited by 37 publications

References 45 publications

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

Fibronectin-Degrading Activity of Trypanosoma cruzi Cysteine Proteinase Plays a Role in Host Cell Invasion

Severity of chronic experimental Chagas' heart disease parallels tumour necrosis factor and nitric oxide levels in the serum: models of mild and severe disease

Current understanding of the Trypanosoma cruzi-cardiomyocyte interaction

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