title: Immunoendocrinology of the thymus in Chagas disease.
abstract: During immune response to infectious agents, the host develops an inflammatory response which could fail to eliminate the pathogen or may become dysregulated. In this case, the ongoing response acquires a new status and turns 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) may also mediate harmful effects. Thymic disturbances seen during Trypanosoma cruzi (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 (DP) CD4+CD8+ population. Thymus cellularity depletion, which occurs in the absence of main immunological mediators involved in anti-T. cruzi defense, seems to be linked to a systemic cytokine/hormonal imbalance, involving a dysregulated increase in Tumor Necrosis Factor alpha (TNF-α) and corticosterone hormone levels. Additionally, we have found an anomalous exit of potentially autoimmune DP cells to the periphery, in parallel to a shrinkage in the compartment of natural 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.
authors.affiliation: Institute of Immunology, School of Medical Sciences, National University of Rosario (U.N.R.), Rosario, Argentina. perez_anarosa @ yahoo.com.ar
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Pérez
authors.forename: Suse Dayse
authors.initials: SD
authors.lastname: Silva-Barbosa
authors.forename: Eduardo
authors.initials: E
authors.lastname: Roggero
authors.forename: Flavia
authors.initials: F
authors.lastname: Calmon-Hamaty
authors.forename: Silvina R
authors.initials: SR
authors.lastname: Villar
authors.forename: Fredy R
authors.initials: FR
authors.lastname: Gutierrez
authors.forename: João Santana
authors.initials: JS
authors.lastname: Silva
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Oscar
authors.initials: O
authors.lastname: Bottasso
mesh_terms: D000486:Allergy and Immunology; D015703:Antigens, CD / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004704:Endocrinology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D013950:Thymus Gland / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D005938:Glucocorticoids