HCV‐infected cells and differentiation increase monocyte immunoregulatory galectin‐9 production

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

关键词: JFH‐;    1;    non‐;    classical monocyte;    exosome;   

DOI  :  10.1189/jlb.5A1214-582R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Thelectingalectin‐9mayhelpestablishandmaintainchronichepatitisCvirusinfection.Galectin‐9iselevatedintheliverandseraofhepatitisCviruspatients,inducesapoptosisofhepatitisCvirus‐specificTcells,andincreasesinhibitoryregulatoryTcells.Kupffercellsstainstronglyforgalectin‐9proteininhepatitisCviruspatients.Inthecurrentstudy,wedeterminedstimulithatinducegalectin‐9productionbymonocytesandmacrophagesinhepatitisCvirusinfection.Withtheuseofreal‐timePCRandflowcytometry,weanalyzedgalectin‐9mRNAandproteinfromhumanmonocytescoculturedwithhepatitisCvirus‐infectedcellsornoninfectioushepatitisCvirussubgenomicrepliconcells.Wefocusedonfindingthestimuliforgalectin‐9production.Additionally,wemeasuredgalectin‐9duringmonocyte‐to‐macrophagematuration.Finally,weexaminedgalectin‐9inperipheralmonocytesfromhepatitisCviruspatientsusingflowcytometry.Galectin‐9mRNAincreased8‐foldwhenprimarymonocyteswereexposedtohepatitisCvirus‐‐infectedcells.MaximuminductionrequiredproximityorcontactanddidnotrequireIFN‐γorhepatitisCvirusvirions.Cocultureofmonocyteswithsubgenomicrepliconcellsincreasedgalectin‐95‐fold,andpurifiedexosomesfrominfectedcellsstimulatedgalectin‐9production.StimulationofmonocyteTLR3,‐7,and‐8increasedgalectin‐9production.Differentiationofmonocytestomacrophagesincreasedgalectin‐9,andnonclassicmonocytesfromhepatitisCviruspatientshadthehighestlevelsofgalectin‐9.HepatitisCvirus‐infectedcellsstimulatedmonocytestoproducegalectin‐9incloseproximity,possibly,inpart,asaresultofexosomesandendosomalTLRs.Differentiationofmonocytestomacrophagesincreasedgalectin‐9.NonclassicmonocytesfromhepatitisCviruspatientsexpressthehighestgalectin‐9levels,suggestingtheymaycontributetoelevatedgalectin‐9andadaptiveimmuneinhibitioninhepatitisCvirusinfection...

【 授权许可】

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