title: Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance.
abstract: C57BL/6 mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease, develop severe thymocyte depletion paralleled by an inflammatory syndrome mediated by tumor necrosis factor-alpha (TNF-alpha). The exacerbated inflammatory reaction induces the activation of hypothalamus-pituitary-adrenal (HPA) axis with the consequent release of corticosterone (CT) into the circulation as a protective response. Thymocyte apoptosis has been related to a rise in TNF-alpha and CT levels, and both mediators are increased in T. cruzi-infected C57BL/6 mice. The depletion of immature CD4(+)CD8(+) thymocytes by apoptosis following infection with the parasite was still present in mice defective in both types of TNF-receptors (double knockout). However, thymic atrophy was prevented by adrenalectomy combined with RU486 administration, demonstrating that this is a CT-driven phenomenon. Our results put emphasis on the importance of an appropriated immuno-endocrine balance during T. cruzi infection and show that functional deviations in the immuno-endocrine equilibrium have profound effects on the thymus and disease outcome.
authors.affiliation: Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100 (2000) Rosario, Argentina.
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Pérez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Roggero
authors.forename: Alicia
authors.initials: A
authors.lastname: Nicora
authors.forename: Jorge
authors.initials: J
authors.lastname: Palazzi
authors.forename: Hugo O
authors.initials: HO
authors.lastname: Besedovsky
authors.forename: Adriana
authors.initials: A
authors.lastname: Del Rey
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Bottasso
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001284:Atrophy; D016516:CD4-CD8 Ratio; D014355:Chagas Disease / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D003345:Corticosterone / Q000097:blood / Q000276:immunology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015735:Mifepristone / Q000494:pharmacology; D015213:Neuroimmunomodulation / Q000276:immunology*; D009490:Neurosecretory Systems / Q000276:immunology / Q000469:parasitology; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics; D013950:Thymus Gland / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D003345:Corticosterone