Quantitative Analysis of Immune Response and Erythropoiesis during Rodent Malarial Infection 英文参考文献.docVIP

QuantitativeAnalysisofImmuneResponseand ErythropoiesisduringRodentMalarialInfection MartinR.Miller1,LarsRa?berg2,AndrewF.Read3,NicholasJ.Savill1* 1CentreforInfectiousDiseases,InstituteofImmunologyandInfectionResearch,UniversityofEdinburgh,Edinburgh,UnitedKingdom,2DepartmentofAnimalEcology, LundUniversity,Lund,Sweden,3CenterforInfectiousDiseaseDynamicsandDepartmentsofBiologyandEntomology,PennsylvaniaStateUniversity,UniversityPark, Pennsylvania,UnitedStatesofAmerica Abstract Malarial infection is associated with complex immune and erythropoietic responses in the host. A quantitative understanding of these processes is essential tohelp inform malaria therapy andfor the designof effective vaccines. In this study, we use a statistical model-fitting approach to investigate the immune and erythropoietic responses in Plasmodium chabaudi infections of mice. Three mouse phenotypes (wildtype, T-cell-deficient nude mice, and nude mice reconstituted with T-cells taken from wildtype mice) were infected with one of two parasite clones (AS or AJ). Under a Bayesianframework,weuseanadaptivepopulation-basedMarkovchainMonteCarlomethodandfitasetofdynamical modelstoobserveddataonparasiteandredbloodcell(RBC)densities.ModelfitsarecomparedusingBayes’factorsand parameterestimatesobtained.Weconsiderthreeindependentimmunemechanisms:clearanceofparasitisedRBCs(pRBC), clearanceofunparasitisedRBCs(uRBC),andclearanceofparasitesthatburstfromRBCs(merozoites).Ourresultssuggest thattheimmuneresponseofwildtypemiceisassociatedwithlessdestructionofuRBCs,comparedtotheimmuneresponse of nude mice. There is a greater degree of synchronisation between pRBC and uRBC clearance than between either mechanismandmerozoiteclearance.Inallthreemousephenotypes,controlofthepeakofparasitedensityisassociated with pRBC clearance. In wildtype mice and AS-infected nude mice, control of the peak is also associated with uRBC clearance.OurresultssuggestthatuRBCclearance,ratherthanRBCinfection,isthemajordeterminantofRBCdynamic