Antimicrobial Peptides and Human Disease PDF
Preview Antimicrobial Peptides and Human Disease
306 Current Topics in Microbiology and Immunology Editors R.W.Compans,Atlanta/Georgia M.D.Cooper,Birmingham/Alabama T.Honjo,Kyoto·H.Koprowski,Philadelphia/Pennsylvania F.Melchers,Basel·M.B.A.Oldstone,LaJolla/California S.Olsnes,Oslo·P.K.Vogt,LaJolla/California H.Wagner,Munich W.M. Shafer (Ed.) Antimicrobial Peptides and Human Disease With12Figuresand4Tables 123 WilliamM.Shafer,Ph.D. DepartmentofMicrobiologyandImmunology 3001RollinsResearchCenter EmoryUniversitySchoolofMedicine Atlanta,GA30322 USA e-mail:[email protected] CoverIllustrationbyDawnM.E.Bowdish,DonaldJ.DavidsonandRobertE.W.Hancock (CoverfigurereproducedwithkindpermissionofLeukemiaResearch)(thisvolume) LibraryofCongressCatalogNumber72-152360 ISSN 0070-217X ISBN-10 3-540-29915-7 SpringerBerlinHeidelbergNewYork ISBN-13 978-3-540-29915-8 SpringerBerlinHeidelbergNewYork Thisworkissubjecttocopyright.Allrightsreserved,whetherthewholeorpartofthematerial isconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation, broadcasting,reproductiononmicrofilmorinanyotherway,andstorageindatabanks.Dupli- cationofthispublicationorpartsthereofispermittedonlyundertheprovisionsoftheGerman CopyrightLawofSeptember,9,1965,initscurrentversion,andpermissionforusemustal- waysbeobtainedfromSpringer-Verlag.ViolationsareliableforprosecutionundertheGerman CopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springeronline.com ©Springer-VerlagBerlinHeidelberg2006 PrintedinGermany Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoes notimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromthe relevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Productliability:Thepublishercannotguaranteetheaccuracyofanyinformationaboutdosage and application contained in this book. In every individual case the user must check such informationbyconsultingtherelevantliterature. Editor:SimonRallison,Heidelberg Deskeditor:AnneClauss,Heidelberg Productioneditor:NadjaKroke,Leipzig Coverdesign:design&productionGmbH,Heidelberg Typesetting:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig Printedonacid-freepaper SPIN11332879 27/3150/YL – 5 4 3 2 1 0 Preface Microbes are in our midst soon after birth. Thankfully, the number of harmless(andoftenbeneficial)microbesfaroutnumberthosethatwoulddo us harm. Our ability to ward off pathogens in our environment, including thosethatcancolonizeourexteriorand/orinteriorsurfaces,dependsonthe integrativeactionoftheinnateandadaptiveimmunitysystems.Thisvolume ofCTMI,entitledAntimicrobialPeptidesandHumanDisease,isdedicatedto theroleofantimicrobialpeptides(AMPs)intheinnatehostdefensesystem ofHomosapiens. Theconceptthatoxygen-independentkillingsystemsofphagocyticcells is in part attributable to the antibiotic-like action of AMPs (and antibacte- rial proteins) stored in cytoplasmic granules served as a stimulus for AMP researchinhumans.Unfortunately,thisearlyworkreceivedlittlenoticeand wasover-shadowedbyinvestigationsoftheoxidativemicrobialkillingcom- ponentsofphagocytes.Onlyahandfuloflaboratorieswereinterestedinthese curiousantimicrobialpeptidesandproteins.However,in1980HansBoman’s group [1] reported on the purification, characterization and antimicrobial actionofanAMPfromanon-humansource–themothHyalophoracecropia, providinganimportantprecedentandacatalystforthefield.Soonthereafter, othergroupsannouncedthepurificationofAMPsfromavarietyofsources includingvertebrates,invertebratesandplants.Itisnowapparentthatallliv- ingsystems(includingmicrobes)havethecapacitytoproduceAMPs.Itisalso clearthatAMPsevolvedlongbeforethedevelopmentofadaptiveimmunity systems, and their induction following injury or infection is a highly con- servedinnateimmuneresponsetomicrobes.Indeed,theyrepresenttheearli- estformofhostdefense.Thus,AMPsareimportantandunderstandingtheir contributiontohostdefensehaspromisefortheadvancementofmedicine. With respect to humans, the groundbreaking work of Lehrer’s group in the early 1980s [2] that characterized the alpha-defensins from human polymorphonuclear leukocytes set the stage for the next 20years of AMP researchasitpertainstothehumaninnateimmuneresponse.Twodecades after the first reports of human neutrophil-derived defensins, we now have abetter,butstillincomplete,understandingoftheAMPrepertoirepossessed byhumans.Lessclear,however,aretheirdirectand/orindirectrolesinhost VI Preface defenseduringinfection.However,considerableprogresshasbeenmadein thisareaandtheseadvancesarehighlightedinseveralchaptersofthisbook. Using small intestinal Paneth cell alpha-defensins as model AMPs, A. Ouellette describes in detail the synthesis and function of AMPs. This systemservesasaverynicemodelthathasrevealedfundamentalinforma- tionregardingtheregulationofAMPgeneexpression, AMPactivationand secretiontotheextracellularfluidinresponsetomicrobes.Whileincreasing evidence implicates the antibiotic-like action of AMPs as being fundamen- tally important in host defense against infection, the immunomodulatory activities ofthesepeptidesisbeingincreasingly appreciated.Undercertain circumstances, these AMP immunomodulatory activities may contribute more to overall host defense than their antimicrobial properties. It is becoming increasingly evident that through their immunomodulatory activitiescertainAMPsconnecttheinnateandadaptiveimmuneresponses, providingwhatmaybeessentiallinksformaintainingtheoverallfidelityof host defense. The wide range and importance of such activities displayed bymembersofthedefensinandcathelicidinpeptidefamilies,thetwomain classesofhumanAMPs,arediscussedindetailbyD.Bowdishetal. ThecontributionofAMPstotheabilityofhumanstodefendthemselves frominfectiousagents,especiallyonrespiratoryandalimentarymucosalsur- faces,areplacedinoverallcontextbyB.AgerberthandG.Gudmundsson.This chaptersetsthestageforaseriesofchaptersthatreviewandhighlightthecon- tributionofAMPstooverallhostdefenseatmanydifferentsites,beginning withthenotionthatAMPsareanessentialcomponentofthedefensivebarrier imposedbyourlargestorgan(skin).AsemphasizedbyM.BraffandR.Gallo, through their bactericidal action and immunomodulatory activities, AMPs havegreatpromiseasfuturistictherapeuticagents.Ifthisgoalisrealized,clin- icianswillhaveanewtreatmentoptionincombatingcommonskinpathogens thatarefrequentlyresistanttomultipleantibiotics.Invasivebloodstreamin- fections are often caused by bacteria that resist multiple antibiotics. These infectionsareresponsibleforasignificantnumberofdeathsworldwideeach year.M.YeamanandA.Bayerdescribehowneutrophil-andplatelet-derived AMPscombatinvasivebloodstreaminfections,andtheyprovidenewinsights astothebiologicimportanceoftheimmunomodulatoryactionofsuchpep- tidesduringbacteremicdisease.Airbornetransmissionofpathogensisama- jormechanismofspreadofinfectiousdiseases.AsishighlightedbyD.Laube etal.,thepresenceandactivityofAMPsarecriticaltotheoverallhealthofthe respiratorytract.Forinstance,thepresenceofAMPsinairwaysurfacefluid (ASF)andtheroleofthesepeptidesinhostdefensehasbeenasubjectofgreat interestinthattheASFfrompatientswithcysticfibrosismaybeinhibitoryfor AMPs,whichmayexplainthesepatients’frequentandoftenlife-threatening Preface VII infections.StrategiesthatoptimizeAMPactivityortheapplicationofAMPs totherespiratorysurfaceepitheliumhavepromiseinhumanmedicineforthe treatmentoflunginfectionsthatarerefractorytoothertreatmentoptions. OnerecurringthemeinmanyofthechaptersinthisvolumeisthatAMPs have functions beyond antimicrobial action. In this respect, hepcidin, a remarkableAMPandapeptidehormonethatisthehomeostaticregulatorof ironavailability,isdiscussedbyT.Ganz.Duringinfectionandinflammation, hepcidinsynthesisisup-regulatedand,becausetheavailabilityoffreeironis criticalforefficientmicrobialgrowth,thepresenceandactionofhepcidincan contribute to host defense. Sexually transmitted infections (STI), including transmissionofthehumanimmunodeficiencyvirus,continuetobeaworld- widepublichealthconcern.Themaleandfemalegenitaltractsaresitesfor AMPproduction,duetotheinfiltrationofphagocyticcellsortheinducible synthesisofAMPsbyepithelialcells.A.Coledescribestheirroleininnatehost defenseagainstSTIswithspecialemphasisonthecontributionofgenitaltract AMPstotheoverallhostdefensivestrategyofprotectingthevaginalmucosal surfacefrominfection.Microbesdonotstandidlybyastheyareassaultedby AMP.Infact,theyhavemechanismstoreduceorthwartthekillingactionof AMP.Inthisrespect,themultiplemechanismsdevelopedbyGram-negative and Gram-positive bacteria to escape or reduce the bactericidal action of AMParereviewedbyA.Peschel.Inrecentyears,wehavecometoappreciate that many pathogens grow in communities and communicate via chemical signals as a population, and bacteria growing in one type of community (biofilms)differsignificantlyfromthosegrowingalone(planktonicgrowth). Thisandtherecognitionthatmicrobialbiofilmsoftenarelesssusceptibleto antimicrobials(includingAMPs)havestimulatedresearcherstounderstand virulencemechanismsthatoperateduringinfectiononhostorimplantsur- faces.M.Ottoreviewsprogressinthisareaofresearchandprovidesinsights regardingnewstrategiestodestroybiofilmformationduringinfection. ThoseofuswhostudyAMPshavebenefitedtremendouslyfromthepio- neeringearlyworkerswhoadvancedfundamentalknowledgeandprinciples regarding critical topics of host defense, infectious diseases, cell biology, biochemistry and pathology. Those accomplishments often were made without the benefit of the instrumentation, techniques, and technologies in molecular biology, biochemistry and cell biology that enabled the field toprogress to its current level. We owe themmuch for their achievements, insightsandprescience.Thisbookisdedicatedtothoseinsightfulscientists andtheiraccomplishments. Atlanta,2005 WilliamM.Shafer VIII Preface References 1. HultmarkD,SteinerH,RasmusonT,BomanHG(1980)Insectimmunity.Purifi- cationandpropertiesofthreeinduciblebactericidalproteinsfromhemolymph ofimmunizedpupaeofHyalophoracecropia.EurJBiochem106:7–16 2. SelstedME,HarwigSS,GanzT,SchillingJW,LehrerRI(1985)Primarystructure ofthreehumanneutrophildefensins.JClinInvest76:1436–1439 ListofContents α PanethCell -DefensinSynthesisandFunction........................ 1 A.J.Ouellette ImmunomodulatoryPropertiesofDefensinsandCathelicidins............. 27 D.M.E.Bowdish,D.J.Davidson,andR.E.W.Hancock HostAntimicrobialDefencePeptidesinHumanDisease.................. 67 B.AgerberthandG.H.Guðmundsson AntimicrobialPeptides: AnEssentialComponentoftheSkinDefensiveBarrier................... 91 M.H.BraffandR.L.Gallo AntimicrobialPeptidesVersusInvasiveInfections ......................111 M.R.YeamanandA.S.Bayer AntimicrobialPeptidesintheAirway ...............................153 D.M.Laube,S.Yim,L.K.Ryan,K.O.Kisich,andG.Diamond Hepcidin—APeptideHormoneattheInterface ofInnateImmunityandIronMetabolism ............................183 T.Ganz InnateHostDefenseofHumanVaginalandCervicalMucosae .............199 A.M.Cole MolecularMechanismsofBacterialResistancetoAntimicrobialPeptides......231 D.KrausandA.Peschel BacterialEvasionofAntimicrobialPeptidesbyBiofilmFormation...........251 M.Otto SubjectIndex................................................259 ListofContributors (Addressesstatedatthebeginningofrespectivechapters) Agerberth,B. 67 Kisich,K.O. 153 Kraus,D. 235 Bayer,A.S. 111 Bowdish,D.M.E. 27 Laube,D.M. 153 Braff,M.H. 91 Otto,M. 251 Cole,A.M. 199 Ouellette,A.J. 1 Davidson,D.J. 27 Peschel,A. 235 Diamond,G. 153 Ryan,L.K. 153 Gallo,R.L. 91 Ganz,T. 183 Yeaman,M.R. 111 Guðmundsson,G.H. 67 Yim,S. 153 Hancock,R.E.W. 27
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