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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/635
Ver los metadatos del registro completo
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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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1844613204664123392 |
score |
13.070432 |