Pathogenesis of chronic Chagas' myocarditis

Rossi, Marcos A.

doi:10.1590/s1516-31801995000200004

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…It is known that during intracellular pathogen-mediated infections, increased pro-inflammatory cytokine production is accompanied by IL-10 production [ 37 , 42 ]. Furthermore, the production of this, anti-inflammatory cytokine was shown to increase in different affected organs, including the heart and kidney, and this production was found to be induced in animals infected with low and high parasitic loads [ 15 , 43 - 45 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load

Vazquez

Miguel

et al. 2015

Parasites Vectors

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BackgroundChagas disease is caused by the protozoan Trypanosoma cruzi and is characterized by cardiac, gastrointestinal, and nervous system disorders. Although much about the pathophysiological process of Chagas disease is already known, the influence of the parasite burden on the inflammatory process and disease progression remains uncertain.MethodsWe used an acute experimental disease model to evaluate the effect of T. cruzi on intestinal lesions and assessed correlations between parasite load and inflammation and intestinal injury at 7 and 14 days post-infection. Low (3 × 102), medium (3 × 103), and high (3 × 104) parasite loads were generated by infecting C57BL/6 mice with “Y”-strain trypomastigotes. Statistical analysis was performed using analysis of variance with Tukey’s multiple comparison post-test, Kruskal–Wallis test with Dunn’s multiple comparison, χ2 test and Spearman correlation.ResultsHigh parasite load-bearing mice more rapidly and strongly developed parasitemia. Increased colon width, inflammatory infiltration, myositis, periganglionitis, ganglionitis, pro-inflammatory cytokines (e.g., TNF-α, INF-γ, IL-2, IL-17, IL-6), and intestinal amastigote nests were more pronounced in high parasite load-bearing animals. These results were remarkable because a positive correlation was observed between parasite load, inflammatory infiltrate, amastigote nests, and investigated cytokines.ConclusionsThese experimental data support the idea that the parasite load considerably influences the T. cruzi-induced intestinal inflammatory response and contributes to the development of the digestive form of the disease.

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Section: Discussionmentioning

confidence: 99%

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load

Vazquez

Miguel

et al. 2015

Parasites Vectors

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“…T. cruzi, the agent of American trypanosomiasis, shows remarkable competence to invade and replicate within the cytoplasm of essentially all of the cell types of its mammalian hosts. Although CD8 ϩ T cell-mediated immunity is critical for protection against T. cruzi infection (13), the parasite manages to survive and establish a chronic infection, which results in myocardiopathy (14). During the acute phase of infection, T. cruzi sheds into the serum large amounts of enzymatically active and inactive proteins belonging to the trans-sialidase (TS) family (15).…”

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confidence: 99%

Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8+ T Cell Responses

Freire-de-Lima

Alisson-Silva

Carvalho

et al. 2010

Journal of Biological Chemistry

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Upon activation, cytotoxic CD8؉ T lymphocytes are desialylated exposing ␤-galactose residues in a physiological change that enhances their effector activity and that can be monitored on the basis of increased binding of the lectin peanut agglutinin. Herein, we investigated the impact of sialylation mediated by trans-sialidase, a specific and unique Trypanosoma transglycosylase for sialic acid, on CD8

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“…Approximately 30% of infected human subjects progress to a severe, diffuse, and fatal chronic myocardiopathy. 22 It is mostly accepted that mononuclear cells, mainly T lymphocytes, are responsible for cardiomyocyte destruction and heart failure in an antigen-dependent manner. However, autoimmunity toward cardiac components 23 and microvascular lesions have also been purposed to be involved in the physiopathology of chagasic heart disease.…”

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confidence: 99%

Fas Ligand-Dependent Inflammatory Regulation in Acute Myocarditis Induced by Trypanosoma cruzi Infection

Oliveira

Diniz

Batista

et al. 2007

The American Journal of Pathology

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Fas/Fas ligand (Fas-L) engagement, a potent inducer of apoptosis, is also important for cellular activation, regulation of effector and chemotactic activity, and secretion of chemokines and cytokines. We evaluated the relevance of Fas/Fas-L in the regulation of myocarditis induced by Trypanosoma cruzi infection and observed that in Fas-L(-/-) mice (gld/gld), cardiac infiltration was significantly reduced, accordingly showing less cardiomyocyte destruction. Fluorescence-activated cell sorting analysis of cardiac inflammatory cells showed higher numbers of CD8(+) T cells in BALB/c compared with gld/gld mice but similar levels of lymphocyte function-associated antigen-1, intercellular adhesion molecule, CD2, and CD69 expression; MAC-1(+) myeloid cells and mast cells were increased in BALB/c mice, whereas gld/gld mice exhibited an enrichment of CD4(+/low) T cells. Intracellular labeling of cytokines revealed no clear cardiac skewing of Th1 or Th2 responses, but we found a higher number of interleukin-10(+) cells in gld/gld mice and a deficient expression of vascular cell adhesion molecule-1 on cardiac endothelial cells in gld/gld mice. Finally, we found a population of CD3(+) but CD4/CD8 double negative cardiac T cells in both groups of infected mice, but down-regulation of some adhesion molecules and surface receptors was only observed in gld/gld mice, indicating a targeted T-cell population mostly affected by the lack of Fas-L engagement. These results point to a role for myocarditis regulation by Fas/Fas-L beyond its possible direct relevance in cellular death.

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Pathogenesis of chronic Chagas' myocarditis

Cited by 10 publications

References 36 publications

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load

Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load

Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8+ T Cell Responses

Fas Ligand-Dependent Inflammatory Regulation in Acute Myocarditis Induced by Trypanosoma cruzi Infection

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