Lack of the programmed death‐1 receptor renders host susceptible to enteric microbial infection through impairing the production of the mucosal natural killer cell effector molecules

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: Citrobacter rodentium;    granzyme B;    perforin;    attaching/effacing bacteria;    PD‐;    1;   

DOI  :  10.1189/jlb.4A0115-003RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Theprogrammeddeath‐1receptorisexpressedonawiderangeofimmuneeffectorcells,includingTcells,naturalkillerTcells,dendriticcells,macrophages,andnaturalkillercells.Inmalignanciesandchronicviralinfections,increasedexpressionofprogrammeddeath‐1byTcellsisgenerallyassociatedwithapoorprognosis.However,itsroleinearlyhostmicrobialdefenseattheintestinalmucosaisnotwellunderstood.Wereportthatprogrammeddeath‐1expressionisincreasedonconventionalnaturalkillercellsbutnotonCD4+,CD8+ornaturalkillerTcells,orCD11b+orCD11c+macrophagesordendriticcellsafterinfectionwiththemousepathogenCitrobacterrodentium.Micegeneticallydeficientinprogrammeddeath‐1ortreatedwithanti–programmeddeath‐1antibodyweremoresusceptibletoacuteentericandsystemicinfectionwithCitrobacterrodentium.Wild‐typebutnotprogrammeddeath‐1–deficientmiceinfectedwithCitrobacterrodentiumshowedsignificantlyincreasedexpressionoftheconventionalmucosalNKcelleffectormoleculesgranzymeBandperforin.Incontrast,naturalkillercellsfromprogrammeddeath‐1–deficientmicehadimpairedexpressionofthosemediators.Consistentwithprogrammeddeath‐1beingimportantforintracellularexpressionofnaturalkillercelleffectormolecules,micedepletedofnaturalkillercellsandperforin‐deficientmicemanifestedincreasedsusceptibilitytoacuteentericinfectionwithCitrobacterrodentium.Ourfindingssuggestthatincreasedprogrammeddeath‐1signalingpathwayexpressionbyconventionalnaturalkillercellspromoteshostprotectionattheintestinalmucosaduringacuteinfectionwithabacterialgutpathogenbyenhancingtheexpressionandproductionofimportanteffectorsofnaturalkillercellfunction...

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