Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries

Detalhes bibliográficos
Autor(a) principal: Lepletier, Ailin
Data de Publicação: 2013
Outros Autores: Carvalho, Vinicius Frias de, Silva, Patrícia Machado Rodrigues e, Villar, Silvina, Pérez, Ana Rosa, Savino, Wilson, Morrot, Alexandre
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/12638
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
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spelling Lepletier, AilinCarvalho, Vinicius Frias deSilva, Patrícia Machado Rodrigues eVillar, SilvinaPérez, Ana RosaSavino, WilsonMorrot, Alexandre2016-01-28T11:22:36Z2016-01-28T11:22:36Z2013LEPLETIER, Ailin; et al. Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries. Plos One, v.7, n.11, 13p, 2013.https://www.arca.fiocruz.br/handle/icict/1263810.1371/journal.pntd.00024701932-6203engPublic Library of ScienceTrypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitriesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.National University of Rosario and CONICET. Faculty of Medical Sciences. Institute of Immunology. Rosario, Argentina.National University of Rosario and CONICET. Faculty of Medical Sciences. Institute of Immunology. Rosario, Argentina.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Rio de Janeiro, RJ, Brasil.We have previously shown that experimental infection caused by Trypanosoma cruzi is associated with changes in the hypothalamus-pituitary-adrenal axis. Increased glucocorticoid (GC) levels are believed to be protective against the effects of acute stress during infection but result in depletion of CD4+ CD8+ thymocytes by apoptosis, driving to thymic atrophy. However, very few data are available concerning prolactin (PRL), another stress-related hormone, which seems to be decreased during T. cruzi infection. Considering the immunomodulatory role of PRL upon the effects caused by GC, we investigated if intrathymic cross-talk between GC and PRL receptors (GR and PRLR, respectively) might influence T. cruziinduced thymic atrophy. Using an acute experimental model, we observed changes in GR/PRLR cross-activation related with the survival of CD4+ CD8+ thymocytes during infection. These alterations were closely related with systemic changes, characterized by a stress hormone imbalance, with progressive GC augmentation simultaneously to PRL reduction. The intrathymic hormone circuitry exhibited an inverse modulation that seemed to counteract the GC-related systemic deleterious effects. During infection, adrenalectomy protected the thymus from the increase in apoptosis ratio without changing PRL levels, whereas an additional inhibition of circulating PRL accelerated the thymic atrophy and led to an increase in corticosterone systemic levels. These results demonstrate that the PRL impairment during infection is not caused by the increase of corticosterone levels, but the opposite seems to occur. Accordingly, metoclopramide (MET)-induced enhancement of PRL secretion protected thymic atrophy in acutely infected animals as well as the abnormal export of immature and potentially autoreactive CD4+ CD8+ thymocytes to the periphery. In conclusion, our findings clearly show that Trypanosoma cruzi subverts mouse thymus homeostasis by altering intrathymic and systemic stress-related endocrine circuitries with major consequences upon the normal process of intrathymic T cell development.Trypanosoma cruziThymic HomeostasisIntrathymic and Systemic StressEndocrine CircuitriesTrypanosoma cruziTimoHomeostaseinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12638/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALvinicius_carvalho_etal_IOC_2013.pdfvinicius_carvalho_etal_IOC_2013.pdfapplication/pdf3865097https://www.arca.fiocruz.br/bitstream/icict/12638/2/vinicius_carvalho_etal_IOC_2013.pdf65caa965de5487006a9dcafcdb9e2293MD52TEXTvinicius_carvalho_etal_IOC_2013.pdf.txtvinicius_carvalho_etal_IOC_2013.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
title Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
spellingShingle Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
Lepletier, Ailin
Trypanosoma cruzi
Thymic Homeostasis
Intrathymic and Systemic Stress
Endocrine Circuitries
Trypanosoma cruzi
Timo
Homeostase
title_short Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
title_full Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
title_fullStr Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
title_full_unstemmed Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
title_sort Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries
author Lepletier, Ailin
author_facet Lepletier, Ailin
Carvalho, Vinicius Frias de
Silva, Patrícia Machado Rodrigues e
Villar, Silvina
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author_role author
author2 Carvalho, Vinicius Frias de
Silva, Patrícia Machado Rodrigues e
Villar, Silvina
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Lepletier, Ailin
Carvalho, Vinicius Frias de
Silva, Patrícia Machado Rodrigues e
Villar, Silvina
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Thymic Homeostasis
Intrathymic and Systemic Stress
Endocrine Circuitries
topic Trypanosoma cruzi
Thymic Homeostasis
Intrathymic and Systemic Stress
Endocrine Circuitries
Trypanosoma cruzi
Timo
Homeostase
dc.subject.decs.pt_BR.fl_str_mv Trypanosoma cruzi
Timo
Homeostase
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-01-28T11:22:36Z
dc.date.available.fl_str_mv 2016-01-28T11:22:36Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv LEPLETIER, Ailin; et al. Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries. Plos One, v.7, n.11, 13p, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/12638
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pntd.0002470
dc.identifier.eissn.none.fl_str_mv 1932-6203
identifier_str_mv LEPLETIER, Ailin; et al. Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries. Plos One, v.7, n.11, 13p, 2013.
10.1371/journal.pntd.0002470
1932-6203
url https://www.arca.fiocruz.br/handle/icict/12638
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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