Stress related hormonal circuitry in Chagas disease

AILIN LEPLETIER; SILVINA VILLAR; ANA ROSA PEREZ; ALEXANDRE MORROT; WILSON SAVINO

Advance in Neuroimmune Biology

IOS Press

Año: 2014

1878-948X

During stress process like the course of infectious disease, neuro, endocrine and immune networksact multi-directionally facilitating the host response; however in exacerbated settingsthis homeostatic mechanism might be altered. In this regard, recent findings emphasize the importance of a balanced neuro-immuno-endocrine network during Chagas disease, caused byTrypanosomacruzi.During the acute immune response againstT. cruzi, the inflammatory and neuro-endocrine response becomesdysregulated with harmful effects for the host. Thymic disturbances seen during T. cruzi infection fit well with this conceptual framework. During infection, this organ suffers a severe atrophy, mainly affecting the immature double positive CD4+CD8+ (DP) population. The depletion of DP cell seems to be linked to a systemic and intrathymic cytokine/hormonal imbalance, involving dysregulated levels of TNF-a, GC and PRL.In addition, these abnormalities are associated to an anomalous exit of potentially autoimmune DP cells to periphery. Furthermore, TNF-áis able to differentially modulate HPA axis: while at central shows stimulatory effects, at adrenal level exert inhibitory actions. Interestingly, chronically infected humans with chagasicmyocardiophatyshowed alterations in HPA and GH-PRL axes. In this context, a better understanding on how disturbances in the flux of information lead to neuroendocrine immune-associated disorderswill provide important insights into mechanisms underlying Chagasdisease pathology.