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Mepacrine介导抗病毒天然免疫功能机制研究和STING调节机制的研究.docx

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Mepacrine介导抗病毒天然免疫功能机制研究和STING调节机制的研究 Mepacrineisawell-knowndrugusedforthetreatmentofmalariaandautoimmunediseases.However,recentstudieshaveshownthatthisdrughasimmunomodulatoryeffectsandcanenhancetheinnateimmuneresponseagainstviralinfections.Inaddition,MepacrinehasbeenfoundtoregulatetheSTINGpathway,whichplaysacrucialroleintheactivationofimmuneresponses.UnderstandingthemechanismsbywhichMepacrinemediatesantiviralinnateimmunefunctionsandregulatestheSTINGpathwayisofgreatimportancefordevelopingnewtherapeuticstrategiesagainstviralinfections. Firstandforemost,innateimmunityservesasthefirstlineofdefenseagainstviralinfections.Thisinnateimmuneresponseisinitiatedbytherecognitionofviralcomponentsbypatternrecognitionreceptors(PRRs).OneofthemajorPRRsinvolvedinantiviralresponsesistheToll-likereceptor(TLR)family,whichrecognizesvariousviralcomponentssuchasviralRNAandDNA.ActivationofTLRsleadstotheproductionofpro-inflammatorycytokinesandtypeIinterferons(IFNs),whicharecrucialfortheclearanceofviralinfections. RecentstudieshaveshownthatMepacrinecanenhancetheantiviralimmuneresponsebyactivatingTLRsignalingpathways.Mepacrinetreatmenthasbeenshowntoincreasetheproductionofpro-inflammatorycytokinesandtypeIIFNsinresponsetoviralinfection.Thisenhancedimmuneresponseleadstothesuppressionofviralreplicationandimprovedviralclearance.Mechanistically,MepacrinehasbeenfoundtotargettheTLRdownstreamsignalingmoleculeIRAK1,leadingtotheactivationofNF-κBandIRF3,whicharemajortranscriptionfactorsresponsiblefortheproductionofpro-inflammatorycytokinesandtypeIIFNs,respectively. Furthermore,MepacrinehasbeenfoundtoregulatetheSTINGpathway,acriticalsignalingpathwayinvolvedintheactivationofimmuneresponsesagainstviralinfections.TheSTINGpathwayisactivatedbytherecognitionofcytosolicviralDNAbythecyclicGMP-AMPsynthase(cGAS),leadingtotheproductionofcyclicGMP-AMP(cGAMP).cGAMPthenbindstoandactivatesSTING,whichsubsequentlytriggerstheproductionoftypeIIFNsandotherimmunemediators.DysregulationoftheSTINGpathwayhasbeenimplicatedinvariou