Thymus atrophy during Trypanosoma cruzi infection is caused by an immuno-endocrine imbalance.
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.
Pérez
Ana Rosa
AR
Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100 (2000) Rosario, Argentina.
Roggero
Eduardo
E
Nicora
Alicia
A
Palazzi
Jorge
J
Besedovsky
Hugo O
HO
Del Rey
Adriana
A
Bottasso
Oscar A
OA
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
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