The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation
Autor: | Ana Rosa Pérez, Juliana de Meis, Maria Cecilia Rodriguez-Galan, Wilson Savino |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Chagas disease Immunology Inflammation Thymus Gland Disease Review Biology medicine.disease_cause cell adhesion and migration Pathogenesis Mice 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Animals Humans Immunology and Allergy Thymocytes Cell Differentiation Epithelial Cells medicine.disease Phenotype Molecular mimicry Thymocyte 030104 developmental biology thymic epithelial cells gene expression thymocyte depletion medicine.symptom lcsh:RC581-607 CD8 030215 immunology |
Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2020) |
ISSN: | 1664-3224 |
Popis: | 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-Vβ 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. |
Databáze: | OpenAIRE |
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