Repetitive Immunization Enhances the Susceptibility of Mice to Peripherally Administered Prions 英文参考文献.docVIP

RepetitiveImmunizationEnhancestheSusceptibilityof MicetoPeripherallyAdministeredPrions JulianeBremer1.,MathiasHeikenwalder1.,JohannesHaybaeck1.,CinziaTiberi1,NikeJuliaKrautler1, MichaelO.Kurrer2,AdrianoAguzzi1* 1Institute of Neuropathology, Department of Pathology, University Hospital of Zurich, Zurich, Switzerland, 2Institute of Pathology, Kantonsspital Aarau, Aarau, Switzerland Abstract The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by geneticmodifiers,andbyhithertounknownhostandenvironmentalriskfactors.Whilelittleisknownaboutthelattertwo, theactivationstateoftheimmunesystemwassurmisedtoinfluenceprionsusceptibility.Hereweadministeredprionsto mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injectionsofbovineserumalbumin/alum.Immunizationgreatlyreducedtherequireddosageofperipherallyadministered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determinediseasepenetranceafterlow-doseprionexposure,includingthosethatmaygiverisetoiatrogenicandvariant Creutzfeldt-Jakobdisease. Citation:BremerJ,HeikenwalderM,HaybaeckJ,TiberiC,KrautlerNJ,etal.(2009)RepetitiveImmunizationEnhancestheSusceptibilityofMicetoPeripherally AdministeredPrions.PLoSONE4(9):e7160.doi:10.1371/journal.pone.0007160 Editor:EtienneJoly,Universite′ deToulouse,France ReceivedJuly7,2009;AcceptedAugust25,2009;PublishedSeptember25,2009 Copyright: ? 2009 Bremer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:AAwassupportedbygrantsoftheBundesamtfuerBildungundWissenschaft,theErnst-Jung-Foundation,theStammbachfoundation,I