Edecio Cunha-Neto

..The bulk of evidence points to a significant production of IFN-gamma and TNF-alpha which may be linked to T. cruzi-induced IL-12 production...

..In this short review, we will discuss the several concepts related to selection of amino acid sequences to be included in DNA and peptide vaccines...

..Furthermore, the distinct recognition repertoire and the high frequency of IFN-gamma producing among CCC patients could be important factors leading to the differential development of CCC among T. cruzi infected individuals...

..The authors will review the evidence in support of an autoimmune basis for CCC pathogenesis in humans and experimental animals, with a special emphasis on molecular mimicry as a fundamental mechanism of autoimmunity...

..It can be hypothesized that cytokine-induced modulation of cardiomyocyte gene/protein expression may be a novel disease mechanism in CCC, in addition to direct inflammatory damage...

..We will review the molecular and immunological mechanisms of myocardial damage in human CCC in light of recent findings...

..Proinflammatory cytokines play a key role in the development of CCC. Clinical, genetic, and epidemiological studies have linked lymphotoxin-alpha (LTA), a proinflammatory cytokine, to coronary artery disease and myocardial infarction...

..BAT1, a putative anti-inflammatory gene, presents functional polymorphisms in its promoter region that influence its transcriptional level...

..This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS...

..cruzi in murine macrophages and to up-regulate the inducible nitric oxide synthase/nitric oxide system, with a consequent increased production of nitric oxide that controls the replication of the parasite...

..The association of TNF genotype with earlier death in CCC should be taken into account when planning therapeutic intervention...

..These results indicate that TNF polymorphisms are associated neither to CCC development nor to progression to more severe forms of cardiomyopathy in Brazilian Chagas disease patients...

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..3-6.0]. The haplotype -262A -62A was prevalent in patients with CCC (40% versus 24%; OR 2.1 [95% CI 1.4-3.3]; Pc=0.0014). The IKBL locus itself or another critical gene in this region may confer susceptibility to the development of CCC...

..3; odds ratio, 15.8). The lack of IL-4 in vitro production by valve-derived HIL also emphasizes the more severe tissue destruction in valves observed in RHD...

..Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction...

..cruzi-infected individuals...

..We tested whether myocarditis, its mediators, and myocardial protein expression are related to the severity of the acute phase of T. cruzi infection in the hamster model...

..Our finding should alert clinicians to the possibility of severe Chagas disease in all regions where T. cruzi circulates, regardless of its lineage...

..This is the first thorough characterization of T cell epitopes of a tandemly repetitive protozoan antigen and may suggest a role for T cell help in the immunodominance of protozoan repetitive antigens...

..The results suggest that direct modulation of myocardium gene and protein expression by inflammatory cytokines may be a new pathogenic mechanism in CCC, with therapeutic implications...

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..cruzi-induced chronic cardiomyopathy and the absence of TNF signaling may be deleterious to the failing heart in Chagas disease cardiomyopathy...

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..6 repeats for binding to chagasic antibodies. These results strengthen previous conclusions on the immunodominant epitope of B13 and provide a comparison of two methods for epitope mapping...

..Even though the Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis, little is known about the factors controlling inflammatory cell migration to CCC myocardium...

..Thus, our results suggest that the recognition of CD8+ T cell epitopes in cruzipain and FL-160 may have a pathogenic or protective role in chronic Chagas disease...

..The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees...

..In addition, the finding of increased anti-B13 IgG levels in sera from CCC patients indicates that clinical presentation is associated with increased anti-B13 antibody levels...

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..In this paper the need for CD4(+) T cell help in vaccine development, the selection of CD4(+) T cell epitopes for an epitope-based vaccine, and how the approach can be used to induce a protective effect are reviewed...

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..Here, we critically review evidence for autoimmune phenomena and their possible pathogenetic role in human Chagas disease and animal models, with a focus on chronic Chagas disease cardiomyopathy...

..IFN-gamma and other cytokine pathways may thus be novel therapeutic targets in Chagas' cardiomyopathy...

..The identified cardiac proteins are likely relevant antigens involved in T cell-mediated autoimmune responses in RF/RHD that may contribute to the development of RHD...

..In Chagas disease, chronic TNF-a production prior to heart failure may play a role in CCC progression...

..brasiliensis. The combination of several such epitopes may increase the frequency of positive responses and allow the immunization of genetically distinct populations...

..We evaluated the role of carvedilol in cardiac remodeling and mortality in a Chagas' cardiomyopathy animal model...

..cruzi -infected human beings...

..This review aims to summarize recent advances in the understanding of the immunopathogenesis of Chagas disease cardiomyopathy...

..The information to be obtained may help develop immune strategies that could be applied to enhance the immune response against mutant HIV-1 and fight the emergence of Pi-resistant HIV-1 strains. ..