| Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
| Phagosomal retention of Francisella tularensis results in TIRAP/Mal‐independent TLR2 signaling | |
| 关键词: macrophage; cytokine; bacterial infection; TLR2; MyD88; | |
| DOI : 10.1189/jlb.0909619 | |
| 学科分类：生理学 | |
| 来源: Federation of American Societies for Experimental Biology | |
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【 摘 要 】
TLR2playsacentralroleintheactivationofinnateimmunityinresponsetoFt,thecausativeagentoftularemia.WereportedpreviouslythatFtLVSelicitedstrong,dose‐dependentNF‐κBreporteractivityinTLR2‐expressinghumanembryokidney293TcellsandthatFtLVS‐inducedmurinemacrophageproinflammatorycytokinegeneandproteinexpressionisTLR2‐dependent.WedemonstratedfurtherthatFtcansignalthroughTLR2fromwithinthephagosomeandthatphagosomalretentionofFtleadstogreatlyincreasedexpressionofasubsetofproinflammatorygenes.ThetwoadaptorproteinsassociatedwithTLR2‐mediatedsignalingareMyD88andTIRAP.AlthoughMyD88isabsolutelyrequiredfortheFt‐inducedmacrophagecytokineresponse,therequirementforTIRAPcanbeovercomethroughretentionofFtwithinthephagosome.TIRAP‐independentsignalingwasobservedwhetherFtwasretainedinthephagosomeasaresultofbacterialmutation(LVSΔiglC)orBFA‐mediatedinhibitionofphagosomeacidification.TherequirementforTIRAPinTLR2signalingcouldalsobeovercomebyincreasingtheconcentrationsofsyntheticbacterialTLR2agonists.Takentogether,thesedatasuggestthatprolongingorenhancingtheinteractionbetweenTLR2anditsagonistovercomesthe“bridging”functionascribedpreviouslytoTIRAP...
【 授权许可】
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【 预 览 】
| Files | Size | Format | View |
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| RO201904049058943ZK.pdf | 631KB |  download |
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