Lipid droplet formation in leprosy: Toll‐like receptor‐regulated organelles involved in eicosanoid formation and Mycobacterium leprae pathogenesis

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

关键词: macrophage;    prostaglandin E2;    foamy cell;    lepromatous leprosy;    mycobacteria;   

DOI  :  10.1189/jlb.0609433

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

AhallmarkofLListheaccumulationofVirchow'sfoamymacrophages.However,theoriginandnatureoftheselipids,aswellastheirfunctionandcontributiontoleprosydisease,remainunclear.WehereinshowthatmacrophagespresentinLLdermallesionsarehighlypositiveforADRP,suggestingthattheirfoamyaspectisatleastinpartderivedfromLD(alsoknownaslipidbodies)accumulationinducedduringMLinfection.Indeed,thecapacityofMLtoinduceLDformationwasconfirmedinvivoviaanexperimentalmodelofmousepleurisyandininvitrostudieswithhumanperipheralmonocytesandmurineperitonealmacrophages.Furthermore,infectedcellswereshowntopropagateLDinductiontouninfected,neighboringcellsbygeneratingaparacrinesignal,forwhichTLR2andTLR6weredemonstratedtobeessential.However,TLR2andTLR6deletionsaffectedLDformationinbacterium‐bearingcellsonlypartially,suggestingtheinvolvementofalternativereceptorsoftheinnateimmuneresponsebesidesTLR2/6forMLrecognitionbymacrophages.Finally,adirectcorrelationbetweenLDformationandPGE2productionwasobserved,indicatingthatML‐inducedLDsconstituteintracellularsitesforeicosanoidsynthesisandthatfoamycellsmaybecriticalregulatorsinsubvertingtheimmuneresponseinleprosy...

【 授权许可】

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