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TRYPANOSOMA CRUZI DISRUPTS THYMIC HOMEOSTASIS BY ALTERING INTRATHYMIC AND SYSTEMIC STRESS-RELATED ENDOCRINE CIRCUITRIES
Thymic Homeostasis
Intrathymic and Systemic Stress
Endocrine Circuitries
Autor
Afiliación
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 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.
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.
Resumen en ingles
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.
Palabras clave en ingles
Trypanosoma cruziThymic Homeostasis
Intrathymic and Systemic Stress
Endocrine Circuitries
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