Pivotal Advance: The promotion of soluble DC‐SIGN release by inflammatory signals and its enhancement of cytomegalovirus‐mediated cis‐infection of myeloid dendritic cells

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

关键词: opsonin;    C‐;    type lectin;    inflammation;   

DOI  :  10.1189/jlb.0710386

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

DC‐SIGNisamemberoftheC‐typelectinfamily.MainlyexpressedbymyeloidDCs,itisinvolvedinthecaptureandinternalizationofpathogens,includinghumanCMV.Severaltranscriptshavebeenidentified,someofwhichcodeforputativesolubleproteins.However,littleisknownabouttheregulationandthefunctionalpropertiesofsuchputativesDC‐SIGNvariants.TobetterunderstandhowsDC‐SIGNcouldbeinvolvedinCMVinfection,wesetouttocharacterizebiochemicalandfunctionalpropertiesofrDC‐SIGNaswellasnaturallyoccurringsDC‐SIGN.Wefirstdevelopedaspecific,quantitativeELISAandthenusedittodetectthepresencesDC‐SIGNininvitro‐generatedDCculturesupernatantsascell‐freesecretedtetramers.Next,incorrelationwiththeirinflammatorystatus,wedemonstratedthepresenceofsDC‐SIGNinseveralhumanbodyfluids,includingserum,jointfluids,andBALs.CMVinfectionofhumantissueswasalsoshowntopromotesDC‐SIGNrelease.Basedontheanalysisofthecytokine/chemokinecontentofsDC‐SIGNculturesupernatants,weidentifiedIFN‐γandCXCL8/IL‐8asinducersofsDC‐SIGNproductionbyMoDC.Finally,wedemonstratedthatsDC‐SIGNwasabletointeractwithCMVgBundernativeconditions,leadingtoasignificantincreaseinMoDCCMVinfection.Overall,ourresultsconfirmthatsDC‐SIGN,likeitswell‐known,counterpartmDC‐SIGN,mayplayapivotalroleinCMV‐mediatedpathogenesis...

【 授权许可】

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