| Author | Pérez, Ana Rosa | |
| Author | Meis, Juliana de | |
| Author | Rodriguez-Galan, Maria Cecilia | |
| Author | Savino, Wilson | |
| Access date | 2021-01-10T18:40:38Z | |
| Available date | 2021-01-10T18:40:38Z | |
| Document date | 2020 | |
| Citation | PÉREZ, 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. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/45552 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Depleção de timócitos | pt_BR |
| Subject in Portuguese | Células epiteliais tímicas | pt_BR |
| Subject in Portuguese | Expressão genetica | pt_BR |
| Subject in Portuguese | Adesão e migração celular | pt_BR |
| Title | The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation | pt_BR |
| Type | Article | |
| DOI | 10.3389/fimmu.2020.01838 | |
| Abstract | Chagas 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. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Instituto de Inmunología Clínica y Experimental de Rosario, CONICET. Rosario, Argentina / Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Centro de Investigación y Producción de Reactivos Biológicos. Rosario, Argentina. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede Rio de Janeiro de Pesquisa em Neuroinflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Inmunología, CIBICI CONICET. Rosario, Argentina. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rede Rio de Janeiro de Pesquisa em Neuroinflamação. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | Thymocyte depletion | pt_BR |
| Subject | Thymic epithelial cells | pt_BR |
| Subject | Gene expression | pt_BR |
| Subject | Cell adhesion and migration | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
