Target Pattern Recognition in Innate Immunity ADVANCESINEXPERIMENTALMEDICINEANDBIOLOGY EditorialBoard: NATHANBACK,StateUniversityofNewYorkatBuffalo IRUNR.COHEN,TheWeizmannInstituteofScience ABELLAJTHA,N.S.KlineInstituteforPsychiatricResearch JOHND.LAMBRIS,UniversityofPennsylvania RODOLFOPAOLETTI,UniversityofMilan RecentVolumesinthisSeries Volume646 EARLYNUTRITIONPROGRAMMINGANDHEALTHOUTCOMESINLATERLIFE EditedbyBertholdKoletzko,TamasDesci,DenesMolnar,andAnneDelaHunty Volume647 THERAPEUTICTARGETSOFTHETNFSUPERFAMILY EditedbyIqbalGrewal Volume648 ARTERIALANDALLIEDCHEMORECEPTORS EditedbyConstancioGonzalez,ColinA.Nurse,andChrisPeers Volume649 MOLECULARMECHANISMSOFSPONDYLOARATHROPATHIES EditedbyCarlosL6pez-Larrea,andRobertoDiaz-Peila Volume650 V(D)JRECOMBINATION EditedbyPierreFerrier Volume651 DEVEOPLMENTANDENGINEERINGOFDOPAMINENEURONS EditedbyR.JeroenPasterkamp,MartenP.Smidt,andJ.PeterH.Burbach Volume652 INHERITEDNEUROMUSCULARDISEASES:TRANSLATIONFROM PATHOMECHANISMSTOTHERAPIES EditedbyCarmenEspin6s,VicenteFelipo,andFrancesePalau Volume653 TARGETPATTERNRECOGNmONININNATEIMMUNITY EditedbyUdayKishore AContinuationOrderPlanisavailableforthisseries.Acontinuationorderwillbringdeliveryofeachnew volumeimmediatelyuponpublication.VolumesarebilledonlyuponactualshipmentForfurtherinformation pleasecontactthepublisher. Target Pattern Recognition in Innate Immunity Editedby UdayKishore,PhD LaboratoryofHumanImmunologyandInfectionBiology, BiosciencesDivision, SchoolofHealth SciencesandSocialCare, BruneiUniversity, Uxbridge, London, UK Springer Science+Business Media, LLC Landes Bioscience SpringerScience+BusinessMedia,LLC LandesBioscience Copyright©2009LandesBioscienceandSpringerScience+BusinessMedia,LLC Allrightsreserved. Nopartofthisbookmaybereproducedortransmittedinanyformorbyanymeans,electronicormechani cal,includingphotocopy,recording,oranyinformationstorageandretrievalsystem,withoutpermission inwritingfromthepublisher,withtheexceptionofanymaterialsuppliedspecificallyforthepurposeof beingenteredandexecutedonacomputersystem;forexclusiveusebythePurchaserofthework. PrintedintheUSA. SpringerScience+BusinessMedia,LLC,233SpringStreet,NewYork,NewYork10013,USA http://www.springer.com Pleaseaddressallinquiriestothepublishers: LandesBioscience,1002WestAvenue,Austin,Texas7870I,USA Phone:51216376050;FAX:51216376079 http://www.landesbioscience.com ThechaptersinthisbookareavailableintheMadameCurieBioscienceDatabase. http://www.landesbioscience.comlcurie Target Pattern Recognition in Innate Immunity edited by Uday Kishore, Landes Bioscience / SpringerScience+BusinessMedia,LLCdual imprint/Springerseries: AdvancesinExperimental MedicineandBiology. 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DEDICATION ToBabujiandmyteachers v FOREWORD Targetpatternrecognitionininnateimmunityisresponsiblefor the immediate, usually protective, responses shownagainstinvadingmicroorganisms, and it is the principalfeatureofselfandnon-selfrecognitionbyvirtueoftherecognitionofstruc turesonthemicrobialpathogens,whicharenotfoundonhostcells.Thisisanarea thathasbeenveryactivelyresearched,overapproximatelythepast 12years,and thereforethisvolumeprovidesatimelycomprehensive,anduptodate,summaryof thetypesandrangeofcellsurface,intracellular,andsecreted,hostproteinsinvolved intherecognitionofmicrobialproducts,andoftheprotectivemechanismstriggered asaresultoftherecognitionevents. TheToll-likereceptors,firstdescribedinDrosophilaandnowwell-character isedonhumancells,provideanexcellentdemonstrationofthewiderangeofdiffer entmicrobialproductsrecognizedbythisfamilyofreceptorsandofthesignalling pathwayswhicharetriggeredthus leadingtoinductionofinflammatorycytokines andtheactivationofgenesproducingantimicrobialproducts. Inaddition, several cell surface proteins involved in target pattern recognition have been described on the surfaces ofmacrophages (macrophagemannose receptorand macrophage scavenger receptors), and on dendritic cells (DEC205), and to be involved with theuptakeandclearanceofwholemicroorganismsandpolyanioicligands.Pattern recognitionisalsoutilisedbyintracellularreceptors,withNOD-likereceptorsinthe cytosolrecognizingmicrobialmoleculesandactivatingtheproductionofinflamma torycytokinesorpathwaysthatinducetheproductionofinflammatorymolecules. Secretedproteins,suchasthepentraxins,whichincludestheacutephasereacting, C-reactiveprotein(CRP)andserumamyloidprotein(SAP),andthecollectins(man nan binding lectin, lung surfactantproteinAand D) and ficolins can also readily recruitkillingandclearancesystems.Indeed,theserumcomplementsystem,which isoneofthemajordefencesystemsinthebloodstream,isefficientlyactivatedby CRPonitsbindingtothephosphocholinegroupsofmicrobialphospholipids-and thesubsequentinteractionoftheboundCRPwithClq-togiveclassicalpathway activation,orMBL,orficolin,bindingtoarraysofmannoseorN-acetyl-glucosamine residues, respectively,onthesurfacesofmicroorganisms-togivelectinpathway activation.Also,inadditiontotheactivationandclearanceeventsassociatedwith vii viii Foreword complementactivationbysomeofthesecretedpatternrecognitionreceptors,itis accepted that all these pattern recognition receptors can generally accelerate the uptakeandclearanceofmicrobesviaphagocyticcells. Inviewofthe growinginterestin thecross-talkbetweeninnateandadaptive immunity,athoroughunderstandingoftheinitialrecognitionandtriggeringevents, mediatedviainnateimmunereceptors,asaddressedinthisvolume,isclearlyvery usefulinhelpingtoalsofullyunderstandthemechanismsofactivationandcontrol oftheadaptiveimmunesystem-andtoallowafullassessmentoftherelativeroles playedbyinnateimmunityandadaptiveimmunityagainstaparticularinfectionin higherorganisms. ProfKennethB.M Reid, FRS Director, MRCImmunochemistryUnit DepartmentofBiochemistry UniversityofOxford Oxford, UK PREFACE Patternrecognitionininnateimmunityhasalwaysfascinatedme.Thedramatic riseinthepopularityandintensityofthisareaofresearchinterestinglycoincidedwith mytimeasapostdoctoralfellowatOxford.WhenIwasaskedbyRonLandesfrom LandesBioscienceifIwouldbe interestedineditingabookonthe title, Ireadily agreed.ItistothecreditofRon,Cynthiaandtheirexcellentteam,andoutstanding contributionsbysomebrilliantscientistsinthefield, thatthisbookisareality. Thefirstchapterdiscussestheimportanceofthemacrophage,itspatternrecog nitionreceptorsanditsrelevancetoinnateimmunity.Thesubsequentchaptershave beenlooselygroupedasreceptorsandsensors (Toll-likereceptorsandNOD-like receptors) andsoluble factors (collectins, pentraxins and complement). There are additionalchaptersthatcollectivelyaddressthemolecularandstructuralorganisa tionsoftheseinnateimmunemolecules.Theroleoftargetpatternrecognitioninthe clearanceofapoptoticcellshasalsobeendiscussed,followedbyDrosophilainnate immunemechanismsasamodelforstudyinginnateimmunity.Finally,twochapters discussingtheinvolvementofinnateimmunityindealingwithtwodevastatingpatho gens, Plasmodium and Mycobacteria, have been included The bookchapters have beenwrittenbywellestablishedandrespectedscientistsintheirrespectivefields of research.Itwasarealdelighttolearnmoreaboutsuchanexcitingfieldwhileediting suchbeautifullycraftedchapters. Thefieldofinnateimmunityhasexpandeddramaticallyinlastdecade.Itsimpact andimportanceonhumanhealthanddiseaseisbeingunderstoodbetterthanever.The understandingoftheabilityoftargetpatternrecognitionmoleculestomodulateand linkwithadaptiveimmuneprocessesviaarangeofmechanismsandpathwayshas beenagenuinerevelation. Notsurprisingly,thisaspectofImmunologyisincreas inglybecomingamajorcomponentofmedicalandmedicine-relatedcurriculum.It islargelyhopedthatthisbookwillbeausefulstartpointforstudents,teachersand activeresearchers. During the course ofplanning and organising this book, Ihave greatly ben efittedfrom myinteractionwithtwoofmymentors(KenReidandBobSim),my colleagues(BrittaUrban,RohitGhai,TrinadChakraborty,TonyTsolakiandPatrick Waters),collaborators(AlokAggrawalandTarunaMadan), andahugenumberof ix x Preface mystudents.Infact,myundergraduateandpostgraduatestudentshavebeenagreat sourceofinspirationtoundertakethisproject.IwouldliketothankRonLandesfor providingmewiththis greatopportunitytoeditabookintheareathatissoclose tomyheart. Isincerelyhopethatthereaderswillfindthisbookinteresting,comprehensive andwellorganised. UdayKishore, PhD LaboratoryofHumanImmunologyandInfectionBiology BiosciencesDivision SchoolofHealthSciencesandSocialCare BruneiUniversity Uxbridge, London, UK