Activation of Indoleamine 2,3-Dioxygenase in Patients with Scrub Typhus and Its Role in Growth Restriction of Orientia tsutsugamushi 英文参考文献.docVIP

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Activation of Indoleamine 2,3-Dioxygenase in Patients with Scrub Typhus and Its Role in Growth Restriction of Orientia tsutsugamushi 英文参考文献.doc

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Activation of Indoleamine 2,3-Dioxygenase in Patients with Scrub Typhus and Its Role in Growth Restriction of Orientia tsutsugamushi 英文参考文献

ActivationofIndoleamine2,3-DioxygenaseinPatients withScrubTyphusandItsRoleinGrowthRestrictionof Orientiatsutsugamushi ThanavadeePrachason1,2,KanitthaKonhan3,PiyapatPongnarin3,SomruedeeChatsiricharoenkul3, YupinSuputtamongkol4,ChaninLimwongse1,5* 1DivisionofMolecularGenetics,DepartmentofResearchandDevelopment,FacultyofMedicine,SirirajHospital,MahidolUniversity,Bangkok,Thailand,2Departmentof Immunology,FacultyofMedicine,SirirajHospital,MahidolUniversity,Bangkok,Thailand,3DepartmentofPharmacology,FacultyofMedicine,SirirajHospital,Mahidol University, Bangkok, Thailand, 4Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand,5DivisionofMedicalGenetics,DepartmentofInternalMedicine,FacultyofMedicine,SirirajHospital,MahidolUniversity,Bangkok,Thailand Abstract Background: Our earlier genome-wide expression study revealed up-regulation of a tryptophan-catabolizing enzyme, indoleamine2,3-dioxygenase(IDO1),inpatientswithscrubtyphus.Thisgenehasbeenpreviouslyreportedtohaveanti- microbialactivityinavarietyofinfectiousdiseases;therefore,weaimedtoprovewhetheritisalsoinvolvedinhostdefense againstOrientiatsutsugamushi(OT)infection. Methodology/Principal Findings: Using LC-MS, we observed an increased ratio of serum L-kynurenine to serum L- tryptophaninpatientswithscrubtyphus,whichsuggestsanactivecatalyticfunctionofthisenzymeupontheillness.To evaluatetheeffectofIDO1activationonOTinfection,ahumanmacrophage-likecelllineTHP-1wasusedasastudymodel. AlthoughtranscriptionofIDO1wasinducedbyOTinfection,itsfunctionalactivitywasnotsignificantlyenhancedunlessthe cellswerepretreatedwithIFN-c,apotentinducerofIDO1.Whenthedegreeofinfectionwasevaluatedbyquantitativereal- time PCR, the relative number of OT 47kDa gene per host genes, or infection index, was markedly reduced by IFN-c treatment as compared to the untreated cultures at five days post-infection. Inhibition of IDO1 activity in IFN-c treated culturesby1