Caspase‐8 and caspase‐9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice

[摘要] Trypanosomacruziacuteinfectionleadstothymicatrophy,largelyasaresultofdeathofimmatureDPTcells.Inasecondvein,theglucocorticoidhormoneimbalancepromotesDPTcellapoptosisininfectedmice.Herein,weassessedtheinvolvementofcaspasesignalinginthymocytedeathduringT.cruziacuteinfection.BALB/cmicewereinfectedi.p.with102trypomastigoteformsofT.cruziandanalyzedfrom7to19dpi.Thymocyteapoptosiswasobservedinearlystagesofinfection,increasingalongwithtimepostinfection.ImmatureDNandDPaswellasCD4+andCD8+thymocytesfrominfectedmiceshowedincreasedactivationofcaspase‐8,‐9,and‐3.Invitrotreatmentofthymocytesfrominfectedmicewithageneralcaspaseinhibitororthecombinationofcaspase‐8‐andcaspase‐9‐specificinhibitorsincreasedthenumberoflivingthymocytes.Intrathymicinjectionofthegeneralcaspaseinhibitor,butnotcaspase‐8or‐9inhibitorsindividually,preventedthymicatrophyandthymocytedepletionininfectedmice.Moreover,blockadeofglucocorticoidreceptoractivitywithRU486preventedDPthymocyteapoptosis,togetherwithcaspase‐8and‐9activation.ThesefindingsindicatethatDPTcellapoptosisfollowingexperimentalT.cruziacuteinfectionisdependentonglucocorticoidstimulation,promotingcaspase‐8and‐9activation...

[学科分类] 生理学

[关键词] thymus;T lymphocytes;Chagas Disease;glucocorticoid;cell death