TLR3 impairment in human newborns

[摘要] Newbornsarehighlysusceptibletoviralinfections.Wehypothesizedthatthissusceptibilitycouldbeduetoadysregulatedexpressionofinnatevirus‐sensingreceptors,i.e.,TLR3,TLR7,TLR8,andTLR9andthecytosolicreceptorsretinoicacid‐induciblegeneI,melanomadifferentiation‐associatedprotein5,proteinkinaseR,andIFN‐γ‐inducibleprotein16.Cordbloodmononuclearcells(CBMCs)expressedmRNAforallthesereceptorsexceptforTLR3.Inperipheralbloodmononuclearcells(PBMCs),TLR3mRNAwaspreferentiallyexpressedincytotoxiccells,particularlyCD56dimNKcells.CordNKcellsincontrastshowedlowTLR3mRNAexpressionandlackedTLR3proteinexpression.CordNKcellsdidnotproduceIFN‐γinresponsetopolyinosinic‐polycytidylicacid[poly(I:C)],whereasstrongIFN‐γproductionwasobservedinpoly(I:C)‐stimulatedadultNKcells.CordNKcellshadpoorcytotoxicfunctionthatwasonlymarginallyenhancedbyexposuretotheTLR3ligandpoly(I:C).OppositetoNKcellsfromadults,theircytotoxicitywasnotimprovedbyherpessimplexvirus(HSV)exposureandtheywereunabletokillHSV‐infectedcells.TherewerenodifferencesintheTLR3mRNAlevelsamongmen,women,andpregnantwomen,implyingthatTLR3isnotundersexhormonecontrol.However,decidualNKcellsexpressedlowlevelsofTLR3mRNA,whichwasattributedtotheirCD56brightphenotype.OurdatashowthatcordbloodNKcellshavedeficientTLR3expressionassociatedwithaninabilitytorespondtopoly(I:C)andHSVactivationandtokillHSV‐infectedcells.ThismightexplainwhynewbornsareparticularlysensitivetoneonatalHSVinfections...

[学科分类] 生理学

[关键词] cord NK cells;poly(I:C);decidual NK cells