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1、Blood.2009February12;113(7):1399–1407.PMCID:PMC2644070Prepublishedonline2008August29.doi:10.1182/blood-2008-07-019307Copyright©2009byTheAmericanSocietyofHematologyReviewArticleTLRsandinnateimmunity1BruceA.Beutler1DepartmentofGenetics,TheScrippsResearchInstitute,LaJolla,CACorrespondingauthor.Rece
2、ivedJuly7,2008;AcceptedAugust15,2008.ThisarticlehasbeencitedbyotherarticlesinPMC.AbstractOneofthemostfundamentalquestionsinimmunologypertainstotherecognitionofnon-self,whichforthemostpartmeansmicrobes.Howdoweinitiallyrealizethatwehavebeeninoculatedwithmicrobes,andhowistheimmuneresponseignited?Ge
3、neticstudieshavemadeimportantinroadsintothisquestionduringthepastdecade,andwenowknowthatinmammals,arelativelysmallnumberofreceptorsoperatetodetectsignaturemoleculesthatheraldinfection.Oneormoreofthesesignaturemoleculesaredisplayedbyalmostallmicrobes.Thesereceptorsandthesignalstheyinitiatehavebee
4、nstudiedindepthbyrandomgermlinemutagenesisandpositionalcloning(forwardgenetics).HereinisaconcisedescriptionofwhathasbeenlearnedabouttheToll-likereceptors,whichplayanessentialpartintheperceptionofmicrobesandshapethecomplexhostresponsesthatoccurduringinfection.OtherSections▼IntroductionWhenitwasf
5、irstrealizedthatmicrobesarethecauseofinfectiousdiseases,anewquestionaroseimmediately.Howaretheydetected?Whatmoleculesareseenasforeign,andwhydowerespondtothem?Thisquestiontouchedonthemolecularbasisofself/non-selfdiscrimination,whichisoftenperceivedasthemostfundamentalquestionofimmunology.Asweunde
6、rstandittoday,self/non-selfdiscriminationhasmanylayers,dependinguponwhichtypeofimmunecellisatissue,orwhattypeof―non-self‖istoberecognized.However,activationofimmuneresponsesishierarchical,andmicrobesarethe―non-self‖withwhichtheimmunesystemevolvedtocope.Assoonastherewasconsensusastotheirinvolveme
7、ntininfectiousdisease,therewasagreatvoidtobefilledinunderstandinghowtheywereinitiallyperceivedbythehostAtoneleveltheanswerwasobvious.Inbiologicsystems,recognitionmostcommonlydependsuponreceptors.Thenotionthattheremustberecep
