Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

Lannes-Vieira, Joseli; Silvério, Jaline Coutinho; Pereira, Isabela Resende; Vinagre, Nathália Ferreira; Carvalho, Cristiano Marcelo Espínola; Paiva, Cláudia N.; Silva, Andréa Alice

doi:10.1590/s0074-02762009000900029

Cited by 28 publications

(21 citation statements)

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“…20 The initial inflammatory response triggered, mainly, by the glycoproteins and other molecules from this protozoan promotes a self-perpetuation of this inflammation, often culminating in a cellular destruction. However, this prominent immune response mediated by innate cells and inflammatory cytokines (e.g., IFN-γ, IL-12, TNF-α, and CCL2), antibodies, and other molecules (e.g., nitric oxide) are necessary to repress parasite replication and invasion.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 But even so, both chemokines have been suggested as good biomarkers of inflammation since their expression in T. cruziinfected heart tissue was detected from as far as 15th to the 240th day of infection. 22,41,42 Indeed, the role of CCL5 in the recruitment of CCR5 plus leukocytes is reinforced by studies where CCR5-deficient mice became more susceptible to T. cruzi infection by the reduction of macrophages and T-cells migration into the heart, especially during early stages of the infection.…”

Section: Discussionmentioning

confidence: 99%

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Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

Penitente¹,

Leite²,

Costa³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

Penitente¹,

Leite²,

Costa³

et al. 2015

The American Journal of Tropical Medicine and Hygiene

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“…In spite of the CD8 + T-cell mediated immune response, the parasite survives within the host and establishes a life-long chronic infection. Parasite persistence is considered one of the critical factors in the development of the complex immunopathology caused by T. cruzi that may occur years after the initial infection in ∼30% of infected individuals [6]–[11]. Thus, understanding how the parasites escape the immune response and persist for such long periods may help us to find new means for interventions against Chagaś disease that would improve quality of life for millions of infected individuals in Latin America…”

Section: Introductionmentioning

confidence: 99%

Subdominant/Cryptic CD8 T Cell Epitopes Contribute to Resistance against Experimental Infection with a Human Protozoan Parasite

et al. 2011

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During adaptive immune response, pathogen-specific CD8+ T cells recognize preferentially a small number of epitopes, a phenomenon known as immunodominance. Its biological implications during natural or vaccine-induced immune responses are still unclear. Earlier, we have shown that during experimental infection, the human intracellular pathogen Trypanosoma cruzi restricts the repertoire of CD8+ T cells generating strong immunodominance. We hypothesized that this phenomenon could be a mechanism used by the parasite to reduce the breath and magnitude of the immune response, favoring parasitism, and thus that artificially broadening the T cell repertoire could favor the host. Here, we confirmed our previous observation by showing that CD8+ T cells of H-2a infected mice recognized a single epitope of an immunodominant antigen of the trans-sialidase super-family. In sharp contrast, CD8+ T cells from mice immunized with recombinant genetic vaccines (plasmid DNA and adenovirus) expressing this same T. cruzi antigen recognized, in addition to the immunodominant epitope, two other subdominant epitopes. This unexpected observation allowed us to test the protective role of the immune response to subdominant epitopes. This was accomplished by genetic vaccination of mice with mutated genes that did not express a functional immunodominant epitope. We found that these mice developed immune responses directed solely to the subdominant/cryptic CD8 T cell epitopes and a significant degree of protective immunity against infection mediated by CD8+ T cells. We concluded that artificially broadening the T cell repertoire contributes to host resistance against infection, a finding that has implications for the host-parasite relationship and vaccine development.

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“…Experiments carried out by Cunha-Neto et al (79) suggest that IFN-γ and CCL2 are related to gene expression of the cardiomyocytes involved in the pathological hypertrophy process. Moreover, the intensity of acute and chronic myocarditis in mice (C3H/He) infected with Colombian strain was directly associated with CCL2 concentration in the heart (80).…”

Section: Darc and Chagas' Diseasementioning

confidence: 96%

Chagas' disease and Duffy antigen/receptor for chemokine (DARC): a mini-review

Oliveira¹,

Mattos²,

Cavasini³

2011

J. Venom. Anim. Toxins incl. Trop. Dis

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Duffy gene (FY) codifies the transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa which is moderately immunogenic. This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system which were designated receptors for chemokines and denominated DARC (Duffy antigen/receptor for chemokine). This receptor has an important role in the regulation of chemokine levels in the circulation, as it binds and adsorbs them on the surface of red cells as a reservoir. It plays a "sink" role, which can contribute to homeostasis by removing inflammatory chemokines from circulation as well as maintaining them in plasmatic levels. Chronic Chagas' cardiopathy (CCC) is the most frequent form of the disease. It is an inflammatory disease, in which infiltrated inflammatory cells play an important role in the development and progress of the infection. High chemokine levels in the plasma have been associated with the disease severity in patients with heart failure. In this context, the profile of DARC expression could play an important function as a receptor for chemokines in Chagas' disease, in patients with CCC, as it can modulate damage from this inflammatory disease.Key words: DARC antigen, Duffy blood-group system, Chagas' disease, Chagas' cardiomyopathy. Review ARticle INTRODUCTIONThe Duffy gene (FY) codifies the moderately immunogenic transmembrane glycoprotein Duffy (gp-Fy) of 35 to 43 kDa (1). This glycoprotein is polymorphic, and constitutes the antigens of the Duffy histo-blood system, which are codified by FYA and FYB alleles of the FY gene playing a codominant role. The FYA and FYB alleles differ due to substitution of the base G by another A in the 125 nucleotide, which develops a common polymorphism in the Caucasian population. This single nucleotide polymorphism (SNP) results in the substitution of amino acid glycine by asparagine in position 42 (2).Although this polymorphism originates distinct glycoproteins called Fya and Fyb antigens, both have moderate immunogenicity.They can be identified with the use of antiFya and anti-Fyb anti-sera, allowing the characterization of four erythrocyte phenotypes: Fy(a+b-), Fy(a-b+), Fy(a+b+) and Fy(a-b-) (3, 4). Negative phenotype Duffy [Fy(a-b-)] is the result of a variant FYB allele (FYB-33), which presents a single point mutation where there is a T to C substitution in nucleotide -33 (-33T>C), also known as the GATA-BOX, located in the promoter region of the FY gene (5, 6).The differential distribution of DARC antigenic determinant between ethnic groups is a characteristic of this histo-blood system. As an example, FYA is prevalent in European, Chinese, Japanese, and Malaysian populations, but rarely in African population. And on the other hand, in Caucasians, FYB is widely found compared to Asian and African populations (7, 8 (25)(26)(27)(28). Genetic mechanisms for the Duffy-negative phenotype in erythrocytes have preserved its expression in the endothelium determining an important role in inflammation physiopathology (16, 19).Antigens...

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Chronic Trypanosoma cruzi-elicited cardiomyopathy: from the discovery to the proposal of rational therapeutic interventions targeting cell adhesion molecules and chemokine receptors - how to make a dream come true

Cited by 28 publications

References 71 publications

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

Subdominant/Cryptic CD8 T Cell Epitopes Contribute to Resistance against Experimental Infection with a Human Protozoan Parasite

Chagas' disease and Duffy antigen/receptor for chemokine (DARC): a mini-review

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