Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance

PEREZ A; ROGGERO E; NICORA A; PALAZZI J; BESEDOVSKY H; DEL REY A; BOTTASSO O

BRAIN BEHAVIOR AND IMMUNITY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2007 vol. 21 p. 890 - 900

0889-1591

C57BL/6 mice infected with Trypanosoma cruzi, the causal agent of Chagas’ disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-a). The exacerbated inflammatory reaction induces the activation of hypothalamus–pituitary–adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-a and CT levels, and both mediators are increased in T. cruziinfected C57BL/6 mice. The depletion of immature CD4+CD8+ thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.Trypanosoma cruzi, the causal agent of Chagas’ disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-a). The exacerbated inflammatory reaction induces the activation of hypothalamus–pituitary–adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-a and CT levels, and both mediators are increased in T. cruziinfected C57BL/6 mice. The depletion of immature CD4+CD8+ thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.