Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria 英文参考文献.docVIP

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Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria 英文参考文献.doc

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Both Functional LTβ Receptor and TNF Receptor 2 Are Required for the Development of Experimental Cerebral Malaria 英文参考文献

BothFunctionalLTbReceptorandTNFReceptor2Are RequiredfortheDevelopmentofExperimentalCerebral Malaria Dieudonne′eTogbe1.,PauloLoureirodeSousa2.,MathildeFauconnier1,VictorineBoissay1 ,Lizette Fick3,StefanieScheu4,KlausPfeffer4,RobertMenard5,GeorgesE.Grau6,Bich-ThuyDoan2,JeanClaude Beloeil2,LaurentRenia6,8,AnnaM.Hansen6,HelenJ.Ball6,NicholasH.Hunt6,BernhardRyffel1*, ValerieF.J.Quesniaux1* 1UniversityofOrle′ans andCNRS,MolecularImmunologyandEmbryologyUMR6218,Orleans,France,2CNRSCBM(CentredeBiophysiqueMole′culaire),Orleans,France, 3Institute of Infectious Disease and Molecular Medicine, Cape Town, South Africa, 4University of Duesseldorf, Duesseldorf, Germany, 5Pasteur Institute Paris, Paris, France, 6The University of Sydney, Department of Pathology, Camperdown, Australia, 7Institut Cochin, Universite′ Paris Descartes, CNRS (UMR 8104), Paris, France, 8Inserm,U567,Paris,France Abstract Background:TNF-relatedlymphotoxina(LTa)isessentialforthedevelopmentofPlasmodiumbergheiANKA(PbA)-induced experimentalcerebralmalaria(ECM).ThepathwayinvolvedhasbeenattributedtoTNFR2.Hereweshowasecondarmof LTa-signalingessentialforECMdevelopmentthroughLTb-R,receptorofLTa1b 2heterotrimer. Methodology/PrincipalFindings:LTbRdeficientmicedidnotdeveloptheneurologicalsignsseeninPbAinducedECMbut diedatthreeweekswithhighparasitaemiaandsevereanemialikeLTabdeficientmice.ResistanceofLTaborLTb Rdeficient micecorrelatedwithunalteredcerebralmicrocirculationandabsenceofischemia,asdocumentedbymagneticresonance imaging and angiography, associated with lack of microvascular obstruction, while wild-type mice developed distinct microvascular pathology. Recruitment and activation of perforin+ CD8 T cells, and their ICAM-1 expression were clearly attenuatedinthebrainofresistantmice.AnessentialcontributionofLIGHT,anotherLTbRligand,couldbeexcluded,as LIGHTdeficientmicerapidlysuccumbedtoECM. + Conclusions/Significance: LTbR expressed on radioresistant resident stromal, probably endothelial cells, rather than hemato