title: Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice.
abstract: Trypanosoma cruzi acute infection leads to thymic atrophy, largely as a result of death of immature DP T cells. In a second vein, the glucocorticoid hormone imbalance promotes DP T cell apoptosis in infected mice. Herein, we assessed the involvement of caspase signaling in thymocyte death during T. cruzi acute infection. BALB/c mice were infected i.p. with 10(2) trypomastigote forms of T. cruzi and analyzed from 7 to 19 dpi. Thymocyte apoptosis was observed in early stages of infection, increasing along with time postinfection. Immature DN and DP as well as CD4(+) and CD8(+) thymocytes from infected mice showed increased activation of caspase-8, -9, and -3. In vitro treatment of thymocytes from infected mice with a general caspase inhibitor or the combination of caspase-8- and caspase-9-specific inhibitors increased the number of living thymocytes. Intrathymic injection of the general caspase inhibitor, but not caspase-8 or -9 inhibitors individually, prevented thymic atrophy and thymocyte depletion in infected mice. Moreover, blockade of glucocorticoid receptor activity with RU486 prevented DP thymocyte apoptosis, together with caspase-8 and -9 activation. These findings indicate that DP T cell apoptosis following experimental T. cruzi acute infection is dependent on glucocorticoid stimulation, promoting caspase-8 and -9 activation.
authors.affiliation: Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Désio Aurélio
authors.initials: DA
authors.lastname: Farias-de-Oliveira
authors.forename: Déa Maria Serra
authors.initials: DM
authors.lastname: Villa-Verde
authors.forename: Pedro Henrique
authors.initials: PH
authors.lastname: Nunes Panzenhagen
authors.forename: Danielle
authors.initials: D
authors.lastname: Silva dos Santos
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Berbert
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Juliana
authors.initials: J
authors.lastname: de Meis
mesh_terms: D000818:Animals; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D014355:Chagas Disease / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000201:enzymology / Q000469:parasitology / Q000473:pathology*; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D014349:Trypanosoma cruzi / Q000276:immunology
chemical_list: D053181:Caspase 8; D053453:Caspase 9