Interleukin‐10 production by myeloid‐derived suppressor cells contributes to bacterial persistence during Staphylococcus aureus orthopedic biofilm infection

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

关键词: MDSC;    IL‐;    10;    macrophage;   

DOI  :  10.1189/jlb.4VMA0315-125RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Staphylococcusaureusisknowntoestablishbiofilmsonmedicaldevices.WerecentlydemonstratedthatLy6GhighLy6C+myeloid‐derivedsuppressorcellsarecriticalforallowingS.aureusbiofilmstosubvertimmune‐mediatedclearance;however,themechanismswherebymyeloid‐derivedsuppressorcellspromotebiofilmpersistenceremainunknown.Interleukin‐10expressionwassignificantlyincreasedinamousemodelofS.aureusorthopedicimplantbiofilminfectionwithkineticsthatmirroredmyeloid‐derivedsuppressorcellrecruitment.Becausemyeloid‐derivedsuppressorcellsproduceinterleukin‐10,weexploredwhetheritwasinvolvedinorchestratingthenonproductiveimmuneresponsethatfacilitatesbiofilmformation.Analysisofinterleukin‐10–greenfluorescentproteinreportermicerevealedthatLy6GhighLy6C+myeloid‐derivedsuppressorcellswerethemainsourceofinterleukin‐10duringthefirst2wkofbiofilminfection,whereasmonocyteshadnegligibleinterleukin‐10expressionuntilday14.Myeloid‐derivedsuppressorcellinfluxintoimplant‐associatedtissueswassignificantlyreducedininterleukin‐10knockoutmiceatday14postinfection,concomitantwithincreasedmonocyteandmacrophageinfiltratesthatdisplayedenhancedproinflammatorygeneexpression.Reducedmyeloid‐derivedsuppressorcellrecruitmentfacilitatedbacterialclearance,asrevealedbysignificantdecreasesinS.aureusburdensinthekneejoint,surroundingsofttissue,andfemurofinterleukin‐10knockoutmice.Adoptivetransferofinterleukin‐10wild‐typemyeloid‐derivedsuppressorcellsintoS.aureus–infectedinterleukin‐10knockoutmicerestoredthelocalbiofilm‐permissiveenvironment,asevidencedbyincreasedbacterialburdensandinhibitionofmonocyteproinflammatoryactivity.Theseeffectswerebothinterleukin‐10‐dependentandinterleukin‐10‐independentbecausemyeloid‐derivedsuppressorcell–derivedinterleukin‐10wasrequiredforpromotingbiofilmgrowthandanti‐inflammatorygeneexpressioninmonocytesbutwasnotinvolvedinmonocyterecruitmenttobiofilm‐infectedtissues.Theseresultsdemonstratethatinterleukin‐10productionbymyeloid‐derivedsuppressorcellscontributestothepersistenceofS.aureusorthopedicbiofilminfections...

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