Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population 英文参考文献.docVIP

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Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population 英文参考文献.doc

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Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population 英文参考文献

GeneticDiversityinCytokinesAssociatedwithImmune VariationandResistancetoMultiplePathogensina NaturalRodentPopulation AndrewK.Turner1*,MikeBegon1,JosephA.Jackson1,2,JanetteE.Bradley3,StevePaterson1 1Institute ofIntegrativeBiology, Biosciences Building,UniversityofLiverpool, Liverpool,United Kingdom, 2Institute ofBiological, Environmental,andRural Sciences, AberystwythUniversity,Aberystwyth,UnitedKingdom,3SchoolofBiology,UniversityofNottingham,Nottingham,UnitedKingdom Abstract Pathogensarebelievedtodrivegeneticdiversityathostlociinvolvedinimmunitytoinfectiousdisease.Todate,studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogenresistancehasrarelybeenexploredinnaturalpopulations.Cytokinesaresignallingmoleculeswitharoleinmany immunologicalandphysiologicalprocesses.Hereweuseanaturalpopulationoffieldvoles(Microtusagrestis)toexamine howgeneticdiversityatasuiteofcytokineandotherimmunelociimpactstheimmuneresponsephenotypeandresistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstratestrongeffectsofgeneticvariationatcytokinelocibothonhostimmunologicalparametersandonresistance tomultiplepathogens.Theseeffectswereprimarilylocalizedtothreecytokinegenes(Interleukin1beta(Il1b),Il2,andIl12b), ratherthantoothercytokinestested,ortomembrane-bound,non-cytokineimmuneloci.Theobservedgeneticeffectswere asgreatasforotherintrinsicfactorssuchassexandbodyweight.Ourresultsdemonstratethatgeneticdiversityatcytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations.Theproductsoftheselociarethereforelikelytoaffectinteractionsbetweenpathogensandhelpdetermine survivalandreproductivesuccessinnaturalpopulations.Ourstudyalsohighlightstheutilityofwildroden