Neisseria meningitidis capsular polysaccharides induce inflammatory responses via TLR2 and TLR4‐MD‐2

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

关键词: capsule;    vaccine;    macrophage;    inflammation;    cytokine;    E5564;   

DOI  :  10.1189/jlb.0610369

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

CPSaremajorvirulencefactorsininfectionscausedbyNeisseriameningitidisandformthebasisformeningococcalserogroupdesignationandprotectivemeningococcalvaccines.CPSpolymersareanchoredinthemeningococcaloutermembranethrougha1,2‐diacylglycerolmoiety,buttheinnateimmunostimulatoryactivityofCPSislargelyunexplored.Well‐establishedhumanandmurinemacrophagecelllinesandHEK/TLRstablytransfectedcellswerestimulatedwithCPS,purifiedfromanendotoxin‐deficientmeningococcalserogroupBNMB‐lpxAmutant.CPSinducedinflammatoryresponsesviaTLR2‐andTLR4‐MD‐2.MeningococcalCPSinducedadose‐dependentreleaseofcytokines(TNF‐α,IL‐6,IL‐8,andCXCL10)andNOfromhumanandmurinemacrophages,respectively.CPSinducedIL‐8releasefromHEKcellsstablytransfectedwithTLR2/6,TLR2,TLR2/CD14,andTLR4/MD‐2/CD14butnotHEKcellsalone.mAbtoTLR2butnotanisotypecontrolantibodyblockedCPS‐inducedIL‐8releasefromHEK‐TLR2/6‐transfectedcells.AsignificantreductioninTNF‐αandIL‐8releasewasseenwhenTHP‐1‐andHEK‐TLR4/MD‐2‐CD14‐butnotHEK‐TLR2‐orHEK‐TLR2/6‐transfectedcellswerestimulatedwithCPSinthepresenceofEritoran(E5564),alipidAantagonistthatbindstoMD‐2,andasimilarreductioninNOandTNF‐αreleasewasalsoseeninRAW264.7cellsinthepresenceofEritoran.CD14andLBPenhancedCPSbioactivity,andNF‐κBwas,asanticipated,themajorsignalingpathway.Thus,thesedatasuggestthatinnateimmunerecognitionofmeningococcalCPSbymacrophagescanoccurviaTLR2‐andTLR4‐MD‐2pathways...

【 授权许可】

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