Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions

Abstract

T cell response plays an essential role in the host resistance to infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. This infection is often associated with multiple manifestations of T cell dysfunction, both during the acute and the chronic phases of disease. Additionally, the normal development of T cells is affected. As seen in animal models of Chagas disease, there is a strong thymic atrophy due to massive death of CD4+CD8+ double-positive cells by apoptosis and an abnormal escape of immature and potentially autoreactive thymocytes from the organ. Furthermore, an increase in the release of corticosterone triggered by T. cruzi-driven systemic inflammation is strongly associated with the alterations seen in the thymus of infected animals. Moreover, changes in the levels of other hormones, including growth hormone, prolactin, and testosterone are also able to contribute to the disruption of thymic homeostasis secondary to T. cruzi infection. In this review, we discuss the role of hormonal circuits involved in the normal T cell development and trafficking, as well as their role on the thymic alterations likely related to the peripheral T cell disturbances largely reported in both chagasic patients and animal models of Chagas disease.

Immunization With Lipopolysaccharide-Activated Dendritic Cells Generates a Specific CD8+ T Cell Response That Confers Partial Protection Against Infection With Trypanosoma cruzi

“…A previous study by our group has shown that males develop a higher parasitemia and show diminished survival when exposed to parasite infection, mainly explained by sexual differences in the regulation of the hypothalamus-pituitary-adrenal axis and the central nervous system ( Roggero et al., 2016 ), as well as differential levels of anti- T. cruzi IgG and IgM (personal communication from Dr. Roggero). Hormonal circuitry, and in particular male hormones, have been implicated in the disruption of thymic homeostasis ( Pérez et al., 2018 ). In this line, another study shows that treatment with Benznidazole present different outcomes depending on mice sex ( Guedes-Da-Silva et al., 2015 ).…”

Longitudinal Speckle Tracking Strain Abnormalities in Chagas Disease: A Systematic Review and Meta-Analysis

“…The reasons behind this specific distribution of myocardial replacement with fibrosis are still unclear; however, it has been suggested that the microvascular derangements characteristic of CCM might cause an ischemic process predominantly in distal areas of the coronary arteries (denominated as watershed zones), potentially explaining the higher frequency of lesions in the LV inferior and inferolateral walls and the apex [ 42 ]. Finally, other pathophysiological mechanisms, such as the derangements in the hypothalamic–pituitary–adrenal axis and specific pathways of iron metabolism, may play a critical role in CCM pathogenesis and progression [ 6 , 43 , 44 ].…”

Infection-Associated Thymic Atrophy

“…Several studies have revealed thymic atrophy during T. cruzi infection. Once infected by T. cruzi, a distinct thymic atrophy occurred with loss of cortical thymocytes, apoptosis of thymocytes (especially DP thymocytes) ( 137 ), migration disturbances, premature exiting of thymocytes, decreased IL-2 level and increased IL-4,5,6, IFN-γ, TNF-α level ( 85 – 87 ). The mechanism underlying premature release of DP thymocytes is being studied.…”