Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes Relationship with Gene Expression in Patients with Scrub Typhus 英文参考文献.docVIP

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Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes Relationship with Gene Expression in Patients with Scrub Typhus 英文参考文献.doc

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Orientia tsutsugamushi Stimulates an Original Gene Expression Program in Monocytes Relationship with Gene Expression in Patients with Scrub Typhus 英文参考文献

OrientiatsutsugamushiStimulatesanOriginalGene ExpressionPrograminMonocytes:Relationshipwith GeneExpressioninPatientswithScrubTyphus WiwitTantibhedhyangkul1,3.,ThanavadeePrachason2,3.,DuangdaoWaywa4,AdilElFilali1,EricGhigo1, WannaThongnoppakhun2,DidierRaoult1,YupinSuputtamongkol4,ChristianCapo1 ,Chanin Limwongse2,4,Jean-LouisMege1* 1Unite′deRecherchesurlesMaladiesInfectieusesTropicalesetEmergentes,CentreNationaldelaRechercheScientifique-InstitutdeRecherchepourleDe′veloppement Unite′ Mixte deRecherche 6236, Universite′ de laMe′diterrane′e, Faculte′ deMe′decine, Marseille, France, 2Division ofMolecular Genetics, Department ofResearchand Development, Mahidol University, Bangkok, Thailand, 3Department of Immunology, Mahidol University, Bangkok, Thailand, 4Department of Medicine, Faculty of MedicineSirirajHospital,MahidolUniversity,Bangkok,Thailand Abstract Orientia tsutsugamushi is the causalagent of scrubtyphus, a public health problem in theAsia-Pacific region anda life- threatening disease. O. tsutsugamushi is an obligate intracellular bacterium that mainly infects endothelial cells. We demonstrated here that O. tsutsugamushi also replicated in monocytes isolated from healthy donors. In addition, O. tsutsugamushialteredtheexpressionofmorethan4,500genes,asdemonstratedbymicroarrayanalysis.Theexpressionof type I interferon, interferon-stimulated genes and genes associated with the M1 polarization of macrophages was significantlyupregulated.O.tsutsugamushialsoinducedtheexpressionofapoptosis-relatedgenesandpromotedcelldeath inasmallpercentageofmonocytes.LiveorganismswereindispensabletothetypeIinterferonresponseandapoptosisand enhancedtheexpressionofM1-associatedcytokines.Thesedatawererelatedtothetranscriptionalchangesdetectedin mononuclearcellsisolatedfrompatientswithscrubtyphus.Here,themicroarrayanalysesrevealedtheupregulationof613 genes, which included interferon-related genes, and some features of M1 polarization were observed in these patients, similartowhatwasobser