Immunoendocrinology of the thymus in Chagas disease

ANA ROSA PÉREZ; SUSE DAYSE SILVA-BARBOSA; EDUARDO ROGGERO; FLAVIA CALMON HAMATY; SILVINA R. VILLAR; FREDY R. GUTIERREZ; JOÃO SANTANA SILVA; WILSON SAVINO; OSCAR BOTTASSO

NEUROIMMUNOMODULATION.

KARGER

Lugar: Basel; Año: 2011 vol. 18 p. 328 - 338

1021-7401

During immune response to infectious agents, the host develops an inflammatory response which could fails to eliminate the pathogen or may become dysregulated. In this case, the ongoing response acquires a new status and turning out to be detrimental. The same elements taking part in the establishment and regulation of the inflammatory response (cytokines, chemokines, regulatory T cells and counteracting compounds like glucocorticoids -GCs-) may also mediate harmful effects. Thymic disturbances seen during T. cruzi infection fit well with this conceptual framework. After infection, this organ suffers a severe atrophy due to apoptosis-induced thymocyte exhaustion, mainly affecting the immature double positive CD4+CD8+ (DP) population. Thymus cellularity depletion, which occurs in the absence of mainly immunological mediators involved in anti Trypanosoma cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance, involving a dysregulated increase in TNF-a and corticosterone hormone levels. Additionally, we have found an anomalous exit of potentially autoimmune DP cells to periphery, in parallel to a shrink in the compartment of naturally regulatory T cells. In this context, our data clearly point to the view that the thymus is a target organ of T. cruzi infection. Preserved thymus may be essential for the development of an effective immune response against T. cruzi, but this organ is severely affected by a dysregulated circuit of proinflammatory cytokines and glucocorticoids. Also, the alterations observed in the DP population might have potential implications for the autoimmune component of human Chagas disease.