Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type

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

关键词: myeloid cells;    fibroblasts;    cytokine;    antiviral;    internalization;   

DOI  :  10.1189/jlb.0312125

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

PolyI:C,asyntheticdsRNAanalogue,hasbeenusedextensivelyfordecadestostudyinnateresponsesinvivoandindifferentcelltypes.WehavefoundsubstantialvariabilitywhileusingpolyI:Cfromdifferentsources.InthisstudywefoundthatpolyI:Cfrom2commercialsourcesinducedsharplyoppositeresponsesinmyeloidandfibroblasts,dependingonthelengthofthepolyI:C.AlthoughshortpolyI:C(∼1–1.5kb)inducedgreateramountsofTNF‐α,IL‐8,andIFN‐βandastrongerantiviralresponseinmyeloidcells,itwasapoorinducerinfibroblasts.Bycontrast,longpolyI:C(>5kb)preferentiallyelicitedhighercytokineandantiviralresponsesinfibroblastsandshoweddiminishedresponsesinmyeloidcells.PolyI:CactivatedNF‐κBandSTAT‐1signalinginalength‐andcell‐type–dependentfashion.Mechanistically,shortpolyI:CwasbetterinternalizedinthemyeloidcellsandlongpolyI:Cinthefibroblasts.Finally,longpolyI:CrequiredSR‐A,whereasshortpolyI:CrequiredRIG‐IandRaftlin.WeprovideevidencethatthelengthofdsRNAdrivesdistinctinnateresponsesindifferentcelllineages.ThesefindingsmayaugmentinselectingtheappropriatepolyI:Ctypetodesigncell‐type–specificpotentadjuvantsforvaccinesagainstinfectiousdiseasesorcancers...

【 授权许可】

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