Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi

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

关键词: IL‐;    17;    IL‐;    23;    Lyme disease;   

DOI  :  10.1189/jlb.4A0715-331R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

WehavepreviouslydemonstratedthatinhibitionofautophagyincreasedtheBorreliaburgdorferiinducedinnatecytokineproductioninvitro,butlittleisknownregardingtheeffectofautophagyoninvivomodelsofBorreliainfection.Here,weshowedthatATG7‐deficientmicethatwereintra‐articularinjectedwithBorreliaspirochetesdisplayedincreasedjointswelling,cellinflux,andenhancedinterleukin‐1βandinterleukin‐6productionbyinflamedsynovialtissue.Becausebothinterleukin‐1βandinterleukin‐6arelinkedtothedevelopmentofadaptiveimmuneresponses,weexaminethefunctionofautophagyonBorreliainducedadaptiveimmunity.Humanperipheralbloodmononuclearcellstreatedwithautophagyinhibitorsshowedanincreaseininterleukin‐17,interleukin‐22,andinterferon‐γproductioninresponsetoexposuretoBorreliaburgdorferi.IncreasedIL‐17productionwasdependentonIL‐1βreleasebut,interestingly,notoninterleukin‐23production.Inaddition,cytokinequantitativetraitlociinATG9BmodulatetheBorreliainducedinterleukin‐17production.BecausehighlevelsofIL‐17havebeenfoundinpatientswithconfirmed,severe,chronicborreliosis,weproposethatthemodulationofautophagymaybeapotentialtargetforanti‐inflammatorytherapyinpatientswithpersistentLymedisease...

【 授权许可】

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