Reduced TNF‐α response in preterm neonates is associated with impaired nonclassic monocyte function

[摘要] Prematureinfantsarehighlysusceptibletoseverebacterialinfections.Theimpairedinfectioncontrolrelatedtothefunctionalimmaturityoftheneonatalinnateimmunesystemisanimportantcauseofinfection.Differentmonocytesubpopulationshavebeendescribedandfunctionallycharacterized.However,datafrompreterminfantsarescarce.WeanalyzedconstitutivemonocyteTLR2,TLR4,CD163,andHLA‐DRexpressioninpretermcordblood.WefurtherinvestigatedactivationofthesignalingproteinsERK1/2andNF‐κBinmonocytesubpopulationsafterexvivostimulationwiththebacterialTLRagonistsLPSandlipoteichoicacid.ThefunctionaloutcomeofthestimulationwasdeterminedbytheintracellularproductionofTNF.Furthermore,thephagocyticactivitywasmeasuredviaflowcytometry.TLR4andHLA‐DRshowedagestationalage‐dependentincrease.However,activationofERK1/2andNF‐κBwasimpairedinneonatalmonocytesubpopulationsafterstimulationwithTLRagonists.Accordingly,intracellularTNFwasdiminishedinpretermmonocytes,especiallyinnonclassicmonocytes.Prematuremonocytesshowedhighphagocyticactivity,withsignificantlyloweracidificationofthephagosome.Thereducedfunctionalresponseofnonclassicmonocytesofpretermneonatesappearstobepartofthediminishedearlyimmuneresponsetobacterialcellwallcomponentsandislikelytocontributetotheirsusceptibilitytobacterialinfection...

[学科分类] 生理学

[关键词] neonatal immunity;Toll‐like receptor;monocytes subsets;very‐low‐birth weight infants