Endogenous ligands of TLR2 and TLR4: agonists or assistants?

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

关键词: PAMP;    DAMP;    innate immunity;    inflammation;    alarmin;   

DOI  :  10.1189/jlb.1209775

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ThemammalianTLRsserveaskeysensorsofPAMPs,suchasbacterialLPS,lipopeptides,andflagellins,whicharepresentinmicrobialcellsbutnothostcells.TLRshavethereforebeenconsideredtoplayacentralroleinthediscriminationbetween“self”and“non‐self”.However,sincethediscoveryoftheirmicrobialligands,manystudieshaveprovidedevidencethathost‐derivedmoleculesmayalsostimulateTLR2‐orTLR4‐dependentsignaling.Todate,morethan20oftheseendogenousTLRligandshavebeenproposed,whichhavetendedtofallintothecategoriesofreleasedintracellularproteins,ECMcomponents,oxidativelymodifiedlipids,andothersolublemediators.ThisreviewaimstosummarizetheevidencesupportingtheintrinsicTLR‐stimulatingcapacityofeachoftheseproposedendogenousligandswithaparticularemphasisonthemeasurestakentoexcludecontaminatingLPSandlipopeptidesfromexperimentalsystems.TheemergingevidencethatmanyofthesemoleculesmaybemoreaccuratelydescribedasPAMP‐bindingmolecules(PBMs)orPAMP‐sensitizingmolecules(PSMs),ratherthangenuineligandsofTLR2orTLR4,isalsosummarized.Therelevanceofthispossibilitytothepathogenesisofchronicinflammatorydiseases,tumorsurveillance,andautoimmunityisdiscussed...

【 授权许可】

CC BY