The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

dc.creatorPérez, Ana Rosa
dc.creatorMeis, Juliana de
dc.creatorRodriguez-Galan, Maria Cecilia
dc.creatorSavino, Wilson
dc.date2021-01-10T18:40:38Z
dc.date2021-01-10T18:40:38Z
dc.date2020
dc.date.accessioned2023-09-26T21:34:36Z
dc.date.available2023-09-26T21:34:36Z
dc.identifierPÉREZ, Ana Rosa et al. The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation. Frontiers in Immunology, v. 11, Article 1838, p. 1-20, Sept. 2020.
dc.identifier1664-3224
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/45552
dc.identifier10.3389/fimmu.2020.01838
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8872871
dc.descriptionChagas disease, caused by the protozoan parasite T. cruzi, is a prevalent parasitic disease in Latin America. Presently, it is spreading around the world by human migration, thus representing a new global health issue. Chronically infected individuals reveal a dissimilar disease progression: while nearly 60% remain without apparent disease for life, 30% develop life-threatening pathologies, such as chronic chagasic cardiomyopathy (CCC) or megaviscerae. Inflammation driven by parasite persistence seems to be involved in the pathophysiology of the disease. However, there is also evidence of the occurrence of autoimmune events, mainly caused by molecular mimicry and bystander activation. In experimental models of disease, is well-established that T. cruzi infects the thymus and causes locally profound structural and functional alterations. The hallmark is a massive loss of CD4+CD8+ double positive (DP) thymocytes, mainly triggered by increased levels of glucocorticoids, although other mechanisms seem to act simultaneously. Thymic epithelial cells (TEC) exhibited an increase in extracellular matrix deposition, which are related to thymocyte migratory alterations. Moreover, medullary TEC showed a decreased expression of AIRE and altered expression of microRNAs, which might be linked to a disrupted negative selection of the T-cell repertoire. Also, almost all stages of thymocyte development are altered, including an abnormal output of CD4−CD8− double negative (DN) and DP immature and mature cells, many of them carrying prohibited TCR-Vb segments. Evidence has shown that DN and DP cells with an activated phenotype can be tracked in the blood of humans with chronic Chagas disease and also in the secondary lymphoid organs and heart of infected mice, raising new questions about the relevance of these populations in the pathogenesis of Chagas disease and their possible link with thymic alterations and an immunoendocrine imbalance. Here, we discuss diverse molecular mechanisms underlying thymic abnormalities occurring during T. cruzi infection and their link with CCC, which may contribute to the design of innovative strategies to control Chagas disease pathology.
dc.formatapplication/pdf
dc.languageeng
dc.publisherFrontiers Media
dc.rightsopen access
dc.subjectDoença de Chagas
dc.subjectDepleção de timócitos
dc.subjectCélulas epiteliais tímicas
dc.subjectExpressão genetica
dc.subjectAdesão e migração celular
dc.subjectChagas Disease
dc.subjectThymocyte depletion
dc.subjectThymic epithelial cells
dc.subjectGene expression
dc.subjectCell adhesion and migration
dc.titleThe Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation
dc.typeArticle


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