Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin‐2 expression

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

关键词: NF‐;    κ;    B;    reactive nitrogen species;    desferrioxamine;    iron;    siderophores;   

DOI  :  10.1189/jlb.1111554

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

TheexpressionofthecationtransporterNramp1(Slc11a1)inlatephagolysosomesconfersresistancetoinfectionwithseveralintracellularpathogens,suchasSalmonellaenterica,inmice.TheantimicrobialactionsofNramp1areattributable,inpart,tomodulationofmacrophageimmunefunctionandcellularironmetabolism—thelatteraffectingtheavailabilityoftheessentialnutrientironforintraphagosomalbacteria.Here,weprovidenovelevidencethatNramp1functionalityincreasestheexpressionofthepeptideLcn2,whichexertsitsantimicrobialactivitybyscavengingiron‐loadedbacterialsiderophoresandmediatingironeffluxfrommacrophages.WiththeuseofmacrophagecelllinesexpressingfunctionalornonfunctionalNramp1,wefoundsignificantlyelevatedLcn2mRNAandproteinlevelsinNramp1‐expressingcells.TheseresultedfromNramp1‐mediatedalterationsintheproductionofROS,whichstimulatedNF‐κBactivityandsubsequently,Lcn2transcription.WeobservedthatincreasedLcn2levelsinprimaryNramp1‐positivemacrophagesresultedinasignificantsuppressionofS.entericaserovartyphimuriumgrowth.StimulationofLcn2expressionisanovelmechanismbywhichNramp1confersresistanceagainstinfectionwiththeintracellularbacteriumS.typhimurium...

【 授权许可】

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