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

Autores
Lepletier, Ailin; Frias de Carvalho, Vinicius; Machado Rodrigues e Silva, Patricia; Villar, Silvina Raquel; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Fil: Lepletier, Ailin. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;
Fil: Frias de Carvalho, Vinicius. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;
Fil: Machado Rodrigues e Silva, Patricia. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;
Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;
Fil: Savino, Wilson. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;
Fil: Morrot, Alexandre. Laboratory of Immunobiology. Paulo de Goes Institute of Microbiology. Federal University of Rio de Janeiro; Brazil;
Materia
Trypanosoma cruzi
Glucocorticoid
Prolactin
Thymus
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/635

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine CircuitriesLepletier, AilinFrias de Carvalho, ViniciusMachado Rodrigues e Silva, PatriciaVillar, Silvina RaquelPerez, Ana RosaSavino, WilsonMorrot, AlexandreTrypanosoma cruziGlucocorticoidProlactinThymushttps://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1We 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 developmentFil: Lepletier, Ailin. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;Fil: Frias de Carvalho, Vinicius. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;Fil: Machado Rodrigues e Silva, Patricia. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;Fil: Savino, Wilson. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;Fil: Morrot, Alexandre. Laboratory of Immunobiology. Paulo de Goes Institute of Microbiology. Federal University of Rio de Janeiro; Brazil;Public Library Science2013-11-14info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/635Lepletier, Ailin; Frias de Carvalho, Vinicius; Machado Rodrigues e Silva, Patricia; Villar, Silvina Raquel; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre; Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries; Public Library Science; Plos Neglected Tropical Diseases; 14-11-2013; 1-13;1935-2735enginfo:eu-repo/semantics/altIdentifier/url/http://www.plosntds.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pntd.0002470&representation=PDFinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:08Zoai:ri.conicet.gov.ar:11336/635instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:38:08.846CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.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
Glucocorticoid
Prolactin
Thymus
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
dc.creator.none.fl_str_mv Lepletier, Ailin
Frias de Carvalho, Vinicius
Machado Rodrigues e Silva, Patricia
Villar, Silvina Raquel
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author Lepletier, Ailin
author_facet Lepletier, Ailin
Frias de Carvalho, Vinicius
Machado Rodrigues e Silva, Patricia
Villar, Silvina Raquel
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author_role author
author2 Frias de Carvalho, Vinicius
Machado Rodrigues e Silva, Patricia
Villar, Silvina Raquel
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
Glucocorticoid
Prolactin
Thymus
topic Trypanosoma cruzi
Glucocorticoid
Prolactin
Thymus
purl_subject.fl_str_mv https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.1
dc.description.none.fl_txt_mv 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
Fil: Lepletier, Ailin. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;
Fil: Frias de Carvalho, Vinicius. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;
Fil: Machado Rodrigues e Silva, Patricia. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Inflammation ; Brazi;
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;
Fil: Perez, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Rosario. Instituto de Inmunología Clínica y Experimental de Rosario; Argentina;
Fil: Savino, Wilson. Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of Thymus Research; Brazil;
Fil: Morrot, Alexandre. Laboratory of Immunobiology. Paulo de Goes Institute of Microbiology. Federal University of Rio de Janeiro; Brazil;
description 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
publishDate 2013
dc.date.none.fl_str_mv 2013-11-14
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/635
Lepletier, Ailin; Frias de Carvalho, Vinicius; Machado Rodrigues e Silva, Patricia; Villar, Silvina Raquel; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre; Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries; Public Library Science; Plos Neglected Tropical Diseases; 14-11-2013; 1-13;
1935-2735
url http://hdl.handle.net/11336/635
identifier_str_mv Lepletier, Ailin; Frias de Carvalho, Vinicius; Machado Rodrigues e Silva, Patricia; Villar, Silvina Raquel; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre; Trypanosoma cruzi Disrupts Thymic Homeostasis by Altering Intrathymic and Systemic Stress-Related Endocrine Circuitries; Public Library Science; Plos Neglected Tropical Diseases; 14-11-2013; 1-13;
1935-2735
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.plosntds.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pntd.0002470&representation=PDF
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432