A Somatically Diversified Defense Factor, FREP3, Is a Determinant of Snail Resistance to Schistosome Infection 英文参考文献.docVIP
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A Somatically Diversified Defense Factor, FREP3, Is a Determinant of Snail Resistance to Schistosome Infection 英文参考文献
ASomaticallyDiversifiedDefenseFactor,FREP3,Isa
DeterminantofSnailResistancetoSchistosomeInfection
PatrickC.Hanington1*,MichelleA.Forys2,EricS.Loker2
1Environmental Health Sciences, School of Public Health, University of Alberta, Edmonton, Alberta, Canada, 2Center for Evolutionary and Theoretical Immunology,
DepartmentofBiology,UniversityofNewMexico,Albuquerque,NewMexico,UnitedStatesofAmerica
Abstract
Schistosomiasis,aneglectedtropicaldisease,owesitscontinuedsuccesstofreshwatersnailsthatsupportproductionof
prolificnumbersofhuman-infectivecercariae.Encountersbetweenschistosomesandsnailsdonotalwaysresultinthesnail
becoming infected, in part because snails can mount immune responses that prevent schistosome development.
Fibrinogen-related protein 3 (FREP3) has been previously associated with snail defense against digenetic trematode
infection. It is a member of a large family of immune molecules with a unique structure consisting of one or two
immunoglobulinsuperfamilydomainsconnectedtoafibrinogendomain;todatefibrinogencontainingproteinswiththis
arrangementarefoundonlyingastropodmolluscs.Furthermore,specificgastropodFREPshavebeenshowntoundergo
somatic diversification. Here we demonstrate that siRNA mediated knockdown of FREP3 results in a phenotypic loss of
resistancetoSchistosomamansoniinfectionin15of70(21.4%)snailsoftheresistantBS-90strainofBiomphalariaglabrata.
Incontrast,noneofthe64controlBS-90snailsreceivingaGFPsiRNAconstructandthenexposedtoS.mansonibecame
infected.Furthermore,resistancetoS.mansoniwasovercomein22of48snails(46%)bypre-exposuretoanotherdigenetic
trematode,Echinostomaparaensei.Lossofresistanceinthiscasewasshownbymicroarrayanalysistobeassociatedwith
strongdown-regulationofFREP3,andothercandidateimmunemolecules.Althoughmanyfactorsarecertainlyinvolvedin
snaildefensefromtrematodeinfection,thisstudyidentifiesforthefirsttimetheinvolvementofaspecificsnailgene,FREP3,
inthephenotypeofresistancetothemedicallyimportantparasite,S.mansoni.Theresultshaveimplicatio
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