Role of TLR2‐dependent IL‐10 production in the inhibition of the initial IFN‐γ T cell response to Porphyromonas gingivalis

[摘要] P.g.,aGram‐negativebacterium,isoneofthemainetiologicalagentsofthechronicinflammatorydisease,periodontitis.Diseaseprogressionisthoughttooccurasaresultofaninadequateimmuneresponse,whichalthoughhappenslocally,canalsooccurdistallyasaresultofthedisseminationofP.g.intothecirculation.AsIL‐10andTLR2arepivotalmoleculesintheimmuneresponsethatP.g.elicits,wehypothesizedthatTLR2‐mediatedIL‐10production,followingtheinitialsystemicexposuretoP.g.,inhibitstheIFN‐γTcellresponse.Toaddressthishypothesis,micewereprimedwithP.g.,andthetypesofcellsproducingIL‐10andthecapacityofTcellstoproduceIFN‐γfollowingblockingorneutralizationofIL‐10wereassessed.OurresultsshowedthatuponinitialencounterwithP.g.,splenicTcellsandCD11b+cellsproduceIL‐10,whichwhenneutralized,resultedinasubstantialincreaseinIFN‐γproductionbyTcells.Furthermore,IL‐10productionwasdependentonTLR2/1signaling,partlyinresponsetothemajorsurfaceprotein,FimAofP.g.Inaddition,P.g.stimulationresultedintheup‐regulationofPD‐1anditsligandPD‐L1onCD4TcellsandCD11b+cells,respectively.Up‐regulationofPD‐1waspartiallydependentonIL‐10butindependentofTLR2orFimA.TheseresultshighlighttheroleofIL‐10ininhibitingTcellresponsestotheinitialsystemicP.g.exposureandsuggestmultipleinhibitorymechanismspotentiallyusedbyP.g.toevadethehostˈsimmuneresponse,thusallowingitspersistenceinthehost...

[学科分类] 生理学

[关键词] cytokine regulation;chronic infections;programmed death 1