Altering Host Resistance to Infections through Microbial Transplantation 英文参考文献.docVIP

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Altering Host Resistance to Infections through Microbial Transplantation 英文参考文献.doc

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Altering Host Resistance to Infections through Microbial Transplantation 英文参考文献

AlteringHostResistancetoInfectionsthroughMicrobial Transplantation BenjaminP.Willing1.,AnjaleeVacharaksa1.,MatthewCroxen1,TeerawatThanachayanont1,B.Brett Finlay1,2 * 1MichaelSmithLaboratories,TheUniversityofBritishColumbia,Vancouver,BritishColumbia,Canada,2DepartmentofMicrobiologyandImmunology,TheUniversityof BritishColumbia,Vancouver,BritishColumbia,Canada Abstract Hostresistancetobacterialinfectionsisthoughttobedictatedbyhostgeneticfactors.Infectionsbythenaturalmurine enteric pathogen Citrobacter rodentium (used as a model of human enteropathogenic and enterohaemorrhagic E. coli infections)varybetweenmicestrains,frommildself-resolvingcolonizationinNIHSwissmicetolethalityinC3H/HeJmice. However,nocleargeneticcomponenthadbeenshowntoberesponsibleforthedifferencesobservedwithC.rodentium infections.Becausetheintestinalmicrobiotaisimportantinregulatingresistancetoinfection,andmicrobialcompositionis dependentonhostgenotype,itwastestedwhethervariationsinmicrobialcompositionbetweenmousestrainscontributed todifferencesin‘‘host’’susceptibilitybytransferringthemicrobiotaofresistantmicetolethallysusceptiblemicepriorto infection.Successfultransferofthemicrobiotafromresistanttosusceptiblemiceresultedindelayedpathogencolonization and mortality. Delayed mortality was associated with increased IL-22 mediated innate defense including antimicrobial peptidesReg3candReg3b,andimmunono-neutralizationofIL-22abrogatedthebeneficialeffectofmicrobiotatransfer. Conversely, depletion of the native microbiota in resistant mice by antibiotics and transfer of the susceptible mouse microbiota resulted in reduced innate defenses and greater pathology upon infection. This work demonstrates the importanceofthemicrobiota andhow itregulates mucosalimmunity,providing animportant factorinsusceptibility to entericinfection.Transferofresistancethroughmicrobialtransplantation(bacteriotherapy)providesadditionalmechanisms toalter‘‘host’’resistance,andanovelmeanstoalterentericinfectionandtostudyhost-pathoge