CONICET | Buscador de Institutos y Recursos Humanos

Immunoendocrine imbalance in murine and human Chagas Disease Wilson Savino1, Ana Rosa Pérez2, Eliane Correa-de-Santana1,3, Alexandre Morrot1,4; Ailin Lepletier de Oliveira1, Suse Dayse Silva-Barbosa1, Oscar Bottasso2. 1Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Immunology Institute, School of Medicine National University of Rosario, Argentina; 3Department of Endocrinology, Max-Planck Institute of Psychiatry, Munich, Germany; 4Department of Immunology, Microbiology Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. We investigated immunoendocrine interactions in mice and humans following infection by Trypanosoma cruzi, the causative agent of Chagas disease. In a first set of experiments, we evaluated the hypothalamuspituitaryadrenal axis of mice undergoing acute or chronic T. cruzi infection. Nests of parasites were seen in the adrenal gland, whereas T. cruzispecific PCR gene amplification product was found in both the adrenal and pituitary glands of acutely infected mice. These endocrine glands also revealed alterations including vascular stasis, increase in the deposition of extracellular matrix (ECM), as well as T cell and macrophage infiltration. Functionally, we found a decrease in corticotrophin-releasing hormone and an increase in corticosterone contents, in hypothalamus and serum, respectively, whereas no significant changes were seen in serum ACTH of infected animals. Nevertheless, the serum levels of interleukin-6 (known to directly stimulate glucocorticoid secretion) were increased, as compared to controls. Circulating ACTH and cortisol levels in chronic chagasic patients remained similar to those seen in healthy subjects. However, DHEA-sulfate decreased as cardiac manifestations increased, with cortisol/DHEA-sulfate ratio being significantly augmented in severe patients. Conjointly, these data strongly point to the existence of abnormal changes of the HPA axis in both murine and human Chagas disease. We then wondered whether the endocrine function of other pituitary cell types could be modified by this parasitic infection, in particular in relation to the production of the prolactin [PRL] and growth hormone [GH]. Studying the mammosomatotrophic cell line GH3, we found a decrease in both GH and PRL secretion. Moreover, we showed that the expression of Pit-1, a major transcription factor for the PRL and GH genes, is decreased in T. cruzi-infected cultures. This was in keeping with the diminished PRL contents seen in the pituitary glands of infected mice. Interestingly, the production of PRL within the thymus (which is also a target organ in Chagas disease) is diminished in T. cruzi infected animals as well. Lastly, in chronically infected patients undergoing mild myocarditis, we also observed a decrease in the circulating levels of both GH and PRL. The work summarized here illustrates the concept that the endocrine system, and in particular those axes controlled by the hypothalamus and pituitary gland, can be considered as a targets in Chagas disease. Yet determining the precise role of such endocrine changes in the pathophysiology of the disease is still open to investigation. Financial Support: Fiocruz, CNPq, Capes; Fundación Ciencias. Médicas Universidad Nacional de Rosario, Argentina.

enviar mensaje