Thymus Atrophy and Double-Positive Escape Are Common Features in Infectious Diseases

Box 1

Box 1. Immunoneuroendocrine interactions involving cytokines and Hypothalamus-Pituitary-Axis in infectious

diseases. Infectious agents lead to activation of innate and adaptive immune response. Proinflammatory

cytokines (IL-1, IL-6, and TNF-α) are key mediators of immune response and stimulate the

Hypothalamus-Pituitary-Adrenal (HPA) axis. This HPA activation leads to increasing corticotrophin-

releasing hormone (CRH) by the hypothalamus and further production of Adrenocorticotropic

hormone (ACTH) by the pituitary gland. ACTH stimulation promotes adrenal production of steroids

as glucocorticoids (GCs), dehydroepiandrosterone (DHEA), and its sulphate ester (DHE). GCs trigger

apoptotic signals to T- and B-cell precursors as well as immature T cells [51–55]. In murine

Chagas disease, there is an imbalance of the HPA axis, with increase in GCs levels, in the absence

of rise in CRH and ACTH [56, 57].