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dc.contributor.author
Perez, Ana Rosa
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dc.contributor.author
de Meis, Juliana
dc.contributor.author
Rodriguez Galan, Maria Cecilia
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dc.contributor.author
Savino, Wilson
dc.contributor.other
Stanislas van Oers, Nicolai
dc.contributor.other
Chidgey, Ann
dc.contributor.other
Dudakov, Jarrod
dc.date.available
2021-11-02T10:53:06Z
dc.date.issued
2020
dc.identifier.citation
Perez, Ana Rosa; de Meis, Juliana; Rodriguez Galan, Maria Cecilia; Savino, Wilson ; The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation; Frontiers Media; 2020; 1-228
dc.identifier.isbn
978-2-88966-268-5
dc.identifier.uri
http://hdl.handle.net/11336/145675
dc.description.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-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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
thymopoiesis
dc.subject
T cell development
dc.subject
thymus regeneration
dc.subject
thymic hypoplasia
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/bookPart
dc.type
info:ar-repo/semantics/parte de libro
dc.date.updated
2021-09-06T20:57:55Z
dc.journal.pagination
1-228
dc.journal.pais
Suiza
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dc.journal.ciudad
Laussanne
dc.description.fil
Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
dc.description.fil
Fil: de Meis, Juliana. Fundación Oswaldo Cruz; Brasil
dc.description.fil
Fil: Rodriguez Galan, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Savino, Wilson. Fundación Oswaldo Cruz; Brasil
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/research-topics/11340/new-insights-into-thymic-functions-during-stress-aging-and-in-disease-settings
dc.conicet.paginas
228
dc.source.titulo
New insights into thymic functions during stress, aging and in disease settings
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