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

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-α). 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-α and CT levels, and both mediators are increased in T. cruzi-infected 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.