Inhibition of dynamin‐dependent endocytosis interferes with type III IFN expression in bacteria‐infected human monocyte‐derived DCs

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: Salmonella;    LPS;    gene;   

DOI  :  10.1189/jlb.1009651

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TypeIIFNs(IFN‐α/βs)andtypeIIIIFNs(IFN‐λ1–3)playanimportantroleinhostdefenseagainstviralinfections.TheinductionoftypeIIFNshasrecentlybeenfoundtotakeplacealsoinbacterialinfections,andtherefore,thisstudyfocusesonanalyzingtheregulationoftypeIIIIFNsinresponsetobacterialstimulation.WefoundbyquantitativeRT‐PCRthattheexpressionofIFN‐λ1andIFN‐λ2/3mRNAs,aswellasthatofIFN‐β,wassimilarlyup‐regulatedinresponsetostimulationwithliveSalmonellatyphimuriumorTLR4agonistLPSinhumanmoDCs.TheinductionofIFN‐λmRNAsdidnotrequireongoingproteinsynthesis,andonlyIFN‐λ1wasdetectedattheproteinlevel.TheinductionofIFN‐λmRNAswassensitivetoSB202190,Ly294002,andPDTC,whichinhibitp38MAPK,PI3K,andNF‐κBactivation,respectively.Furthermore,weobservedthatblockingdynamin‐dependentendocytosispathwayswithdynasoreledtodecreasedcellsurfaceexpressionofCD86andHLAclassIImoleculesandreducedproductionofIFN‐λ1,CXCL10,andIL‐6whenthecellswereinfectedwithS.typhimurium.Cytokineproductionwasalsoimpairedindynasore‐treated,Streptococcusthermophilus‐stimulatedcells.Further,inhibitionofdynaminpreventedS.typhimurium‐inducedphosphorylationofIRF3andtheinternalizationofthebacteria.Insummary,inductionoftypeIIIIFNsinbacteria‐infectedhumanmoDCsrequiresmultiplesignalingpathwaysandinvolvesbacterialphagocytosis...

【 授权许可】

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