CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

Marino, Ana Paula M.P.; Silva, Andréa Alice; Santos, Paula V.A. dos; Pinto, Luzia M. O.; Gazinelli, R. T.; Teixeira, Mauro Martins; Lannes-Vieira, Joseli

doi:10.1590/s0074-02762005000900015

Cited by 25 publications

(18 citation statements)

References 39 publications

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“…The major challenge in designing an efficacious treatment for T. cruzi-elicited myocarditis is that any strategy must be able to decrease the intense inflammation, which produces severe tissue damage, without hampering the host's ability to control the parasite load (Marino et al 2005). The currently available therapeutic options for CD are limited.…”

Section: Discussionmentioning

confidence: 99%

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

Rodrigues

Miguel

Chica

et al. 2010

Mem. Inst. Oswaldo Cruz

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The acute phase of Trypanosoma cruzi infection is associated with a strong inflammatory reaction in the heart characterised by a massive infiltration of immune cells that is dependent on the T. cruzi strain and the host response. 15d-PGJ2 belongs to a new class of anti-inflammatory compounds with possible clinical applications. We evaluated the effects of 15d-PGJ2 administered during the acute phase of T. cruzi infection in mice. Mice were infected with the Colombian strain of T. cruzi and subsequently treated with 15d-PGJ2 repeatedly for seven days. The inflammatory infiltrate was examined by histologic analysis. Slides were immunohistochemically stained to count the number and the relative size of parasite nests. Infection-induced changes in serum cytokine levels were measured by ELISA. The results demonstrated that treatment with 15d-PGJ2 reduced the inflammatory infiltrate in the skeletal muscle at the site of infection and decreased the number of lymphocytes and neutrophils in the blood. In addition, we found that 15d-PGJ2 led to a decrease in the relative volume density of amastigote nests in cardiac muscle. T. cruzi-infected animals treated with 15d-PGJ2 displayed a statistically significant increase in IL-10 levels with no change in IFN-γ levels. Taken together, we demonstrate that treatment with 15d-PGJ2 in the acute phase of Chagas disease led to a controlled immune response with decreased numbers of amastigote nests, as measured by the volume density

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Section: Discussionmentioning

confidence: 99%

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

Rodrigues

Miguel

Chica

et al. 2010

Mem. Inst. Oswaldo Cruz

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“…Other inflammatory mediators and chemokines such as IL-18 and CCR7 ligands, upmation in response to chemokines such as CCL2, CCL3, CCL4, CCL5, CXCL10 and CCR5 [41] . The blockade of one, CCR5, by Met-RANTES significantly decreased the intensity of cardiac inflammatory infiltrate, suggesting that lymphocyte migration to the myocardium during acute infection is dependent on CCR5 ligands [42,43] . IFN-γ-inducible adhesion molecules, such as fibronectin and VCAM-1, can also be detected at high levels in cardiac tissue from T. cruzi-infected mice [44] .…”

Section: Ifn-γ Acts As An Immunological Mediator Inducing Protection mentioning

confidence: 97%

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Ferreira¹,

Frade²,

Baron³

et al. 2014

WJC

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Chagas disease cardiomyopathy (CCC), the main consequence of Trypanosoma cruzi (T.cruzi ) infection, is an inflammatory cardiomyopathy that develops in up to 30% of infected individuals. The heart inflammation in CCC patients is characterized by a Th1 T cell-rich myocarditis with increased production of interferon (IFN)-γ, produced by the CCC myocardial infiltrate and detected at high levels in the periphery. IFN-γ has a central role in the cardiomyocyte signaling during both acute and chronic phases of T.cruzi infection. In this review, we have chosen to focus in its pleiotropic mode of action during CCC, which may ultimately be the strongest driver towards pathological remodeling and heart failure. We describe here the antiparasitic protective and pathogenic dual role of IFN-γ in Chagas disease.

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“…A growing concern is our understanding of these coinfections, which demand further investigations in regions of the world where this disease is both endemic and not endemic (410). In this respect, a comprehension of the pathogeneses of coinfections involved is crucial for the delivery of new therapeutic strategies, and chemokine receptors may become important therapeutic targets for immunosuppressed patients (263).…”

Section: Immunosuppressionmentioning

confidence: 99%

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

et al. 2011

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SUMMARY Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8 + γδ, and CD8α + T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease.

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CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi-elicited myocarditis

Cited by 25 publications

References 39 publications

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

15d-PGJ2 modulates acute immune responses to Trypanosoma cruzi infection

Interferon-γ and other inflammatory mediators in cardiomyocyte signaling during Chagas disease cardiomyopathy

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

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