Antibodies against Marinobacter algicola and Salmonella typhimurium Flagellins Do Not Cross-Neutralize TLR5 Activation 英文参考文献.docVIP

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Antibodies against Marinobacter algicola and Salmonella typhimurium Flagellins Do Not Cross-Neutralize TLR5 Activation 英文参考文献.doc

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Antibodies against Marinobacter algicola and Salmonella typhimurium Flagellins Do Not Cross-Neutralize TLR5 Activation 英文参考文献

AntibodiesagainstMarinobacteralgicolaandSalmonella typhimuriumFlagellinsDoNotCross-NeutralizeTLR5 Activation RaulTerron-Exposito1,BenoitDudognon2,InmaculadaGalindo1,JoseI.Quetglas3,JulioM.Coll1, JoseM.Escribano1,EduardoGomez-Casado1* 1DepartmentofBiotechnology,InstitutoNacionaldeInvestigacio′nyTecnolog?′aAgrariayAlimentaria,INIA,Madrid,Spain,2AlternativeGeneExpressionS.L.(ALGENEX S.L.),Madrid,Spain,3DivisionofGeneTherapy,CentrodeInvestigacio′nenMedicinaAplicada,CIMA,Pamplona,Spain Abstract Flagellinsevokestronginnateandadaptiveimmuneresponses.Theseproteinsmayplayakeyroleasradioprotectors,exert antitumoralactivityincertaintypes oftumorandreducegraft-versus-hostdiseaseinallogeneichematopoieticstemcell transplantrecipients.Notwithstanding,flagellinsarehighlyimmunogenic,andrepeateduseleadstotheirneutralizationby systemicantibodies.Thisneutralizationisnotpreventedbyusingfunctionaldeletedflagellins.Theseobservationsledusto explorethepossibilityofpreventinginitialneutralizationbymeansofanotherfunctionalflagellinthatdoesnotbelongto commonpathogenicbacteriabutthathasthecapacitytoactivateTLR5.Herewecharacterizedthefunctionalcapacityof thetwo-phaseMarinobacteralgicola(MA)-derivedflagellins(FandFR)assystemicandmucosaladjuvantsandcompared theirperformancewiththatofSalmonellatyphimurium(STF)flagellins(FljBandFliC).Wealsoreportforthefirsttimeonthe invitroandinvivocapacityofvariousflagellinstotriggerTLR5activationinthepresenceofspecies-specificanti-flagellin antibodies, the cross-neutralization mediated by these antibodies, and the sequential use of these flagellins for TLR5 activation.OurresultsshowedthatMAflagellinsbehaveinasimilarwaytoSTFones,inducingpro-inflammatorycytokines (IL8,CCL20,CCL2)andevokingastronginvivoantibodyresponseagainstamodelepitope.Moreimportantly,MAflagellins werefullyfunctional,invitroorinvivo,inthepresenceofahighconcentrationofneutralizinganti-flagellinSTFantibodies, and STF flagellin was not inhibited by neutralizing anti-flagellin MA antibodies. The u