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Consequences of immunosenescence against the experimental infection by Trypanosoma cruzi

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Author(s):
Rafaela Pravato Colato
Total Authors: 1
Document type: Doctoral Thesis
Press: Ribeirão Preto.
Institution: Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC)
Defense date:
Examining board members:
Jose Clovis do Prado Junior; Fernanda de Freitas Anibal; Janete Aparecida Anselmo Franci; Patricia Moreira Gomes; Rosely dos Santos Malafronte; Angelita Maria Stabile
Advisor: Jose Clovis do Prado Junior; Gabriela Silva Bisson
Abstract

Despite all the scientific advances in the last decades, Chagas disease is still an important public health problem. Every year, the life expectancy in Brazil has increased and this growth tops with the emergence of an elderly population at risk of contracting this disease. Therefore, the objectives of this study were to evaluate the immune response in senescent Wistar rats, infected with T. cruzi Y strain. Changes in innate immunity was observed in the population of peritoneal macrophages, as well as signaling (RT1B expression) and the costimulatory molecule (CD80) of APC cells in senile animals. Cellular immunity was also reduced, since senile animals showed a significant decrease in the percentage of CD4+ T and CD8+T lymphocytes when compared to young counterparts. A reduced expression of the major signaling molecule, CD28+, responsible for T cell activation was also observed as long as animals age. Aging was associated with an increase in the percentage of CD25+ CD25lowFOXP3+ lymphocytes, which represent T regulator cells. On the other hand, the uninfected senile animals presented a significant reduction in the percentage of CD4+ CD25highFOXP3+ lymphocytes. Senescence as well as the infectious process triggered an increase in corticosterone levels and in the percentage of splenocytes in early and late apoptosis in senile infected animals. Aging also negatively regulated the DN1-DN2 transition, as well as the subpopulations of thymocytes DN3 and DN4 in senile animals, infected or not. A reduction in the percentage of viable thymocytes was observed in control and infected senile animals. Regarding to oxidative stress, aging increased the levels of TBARS, reduced the activity of the main antioxidant enzyme SOD and the concentration of 8-isoprostane. Oppositely, aged animals displayed increased levels of the enzyme glutathione peroxidase GSH as compared to the young ones. The analysis of cytokine production evidenced an increase in TGF-? levels in senile animals. On the 16th day after infection, enhanced concentrations of IL-12 was observed only in senile infected animals. However, this same group showed a reduction in IL-2 production on the 9th day after infection. Senile and control animals displayed higher IL-17 concentrations when compared to young animals. Both T. cruzi infection and aging caused an increase in TNF-? levels in young and senile infected animals. The present study allowed us to better understand the cellular and molecular mechanisms involved in the immune response throughout life and its actions on Chagas\' disease. For that, several alterations were observed such as an inefficient immune response, increased oxidative stress, decreased antioxidant enzyme activity and impairment in the intratymic cell maturation process, impairing thymocyte development and the export of T cells to the periphery, as well decreased cell viability. A functional imbalance of the neuroendocrine axis was also observed, as well as changes in the profile of cytokine production directly impairing the immune competence in these animals. (AU)

FAPESP's process: 14/00303-6 - Immunosenescence: impact against the experimental infection with Trypanosoma cruzi
Grantee:Rafaela Pravato Colato
Support Opportunities: Scholarships in Brazil - Doctorate