THYMUS ALTERATIONS DURING TRYPANOSOMA CRUZI INFECTION

ANA ROSA PÉREZ

Dresden

Conferencia; 8th International Congress of the International Society of Neuroimmunomodulation; 2011

International society for Neuroimmunomodulation

Several alterations in the different T cell compartments were observed during experimental T. cruzi infection, the causal agent of Chagas disease. In particular, the thymus, the organ responsible for development of mature T CD4+, CD8+ (SP) and CD4+CD25+FoxP3+ regulatory T cells, suffers a severe atrophy. This atrophy is due to apoptosis, mainly affecting double positive CD4+CD8+ (DP) cells, the immature precursors of SP and regulatory T cells. Such loss is more profound in animals failing to control parasite infection and seems to be linked to a systemic immunoendocrine imbalance, involving a dysregulated increase in TNF-a and corticosterone levels. We have also found an anomalous exit of DP immature T cells to the periphery in parallel to an enhanced intrathymic deposition of molecules related with migratory processes. It is unknown whether thymic abnormalities occur in T. cruzi infected patients; nevertheless, our preliminary data suggest that immature cell escape occurs even during chronic phase in these individuals. Turning to the mouse model, we also noted that SP and immature thymocytes from T. cruzi-infected mice exhibit an increased migratory response to TNF-a when bound to fibronectin. We also detect a progressive shrink in the CD4+CD25+FoxP3+regulatory cells, which may affect the peripheral replenish of this population. Collectively, our data clearly point that the immunoendocrine response against T. cruzi, is unsuccessful to counteract the inflammatory reaction, fails to promote pathogen control, and becomes dysregulated with harmful effects on the thymus. In turn, altered thymus homeostasis may impede the development of an effective immune response against T. cruzi and favoring the autoimmune component of Chagas disease.