Porphyromonas gingivalis suppresses adaptive immunity in periodontitis, atherosclerosis, and Alzheimer’s disease

摘要

Porphyromonasgingivalis,akeystonepathogeninchronicperiodontitis,hasbeenfoundtoassociatewithremotebodyorganinflammatorypathologies,includingatherosclerosisandAlzheimer’sdisease(AD).AlthoughP.gingivalishasaplethoraofvirulencefactors,muchofitspathogenicityissurprisinglyrelatedtotheoverallimmunosuppressionofthehost.ThisreviewfocusesonP.gingivalisaidingsuppressionofthehost’sadaptiveimmunesysteminvolvingmanipulationofcellularimmunologicalresponses,specificallyTcellsandBcellsinperiodontitisandrelatedconditions.Inperiodontitis,thisbacteriuminhibitsthesynthesisofIL-2andincreaseshumoralresponses.ThisreducestheinflammatoryresponsesrelatedtoT-andB-cellactivation,andsubsequentIFN-γsecretionbyasubsetofTcells.TheTcellsfurthersuppressupregulationofprogrammedcelldeath-1(PD-1)-receptoronCD+cellsanditsligandPD-L1onCD11b+-subsetofTcells.IL-2downregulatesgenesregulatedbyimmuneresponseandinducesacytokinepatterninwhichtheTh17lineageisfavored,therebymodulatingtheTh17/T-regulatorycell(Treg)imbalance.ThesuppressionofIFN-γ-stimulatedreleaseofinterferon-inducibleprotein-10(IP-10)chemokineligands[ITAC(CXCL11)andMig(CXCL9)]byP.gingivaliscapsularserotypestriggersdistinctTcellresponsesandcontributestolocalimmuneevasionbyreleaseofitsoutermembranevesicles.Inatherosclerosis,P.gingivalisreducesTregs,transformsgrowthfactorbeta-1(TGFβ-1),andcausesimbalanceintheTh17lineageoftheTregpopulation.InAD,P.gingivalismayaffecttheblood–brainbarrierpermeabilityandinhibitlocalIFN-γresponsebypreventingentryofimmunecellsintothebrain.ThescarcityofadaptiveimmunecellsinADneuropathologyimpliesP.gingivalisinfectionofthebrainlikelycausingimpairedclearanceofinsolubleamyloidandinducingimmunosuppression.Bytheeffectivemanipulationofthearmoryofadaptiveimmunesuppressionthroughaplethoraofvirulencefactors,P.gingivalismayactasakeystoneorganisminperiodontitisandinrelatedsystemicdiseasesandotherremotebodyinflammatorypathologies.Keywords:P.gingivalis;adaptiveimmunity;suppression;periodontitis;atherosclerosis;Alzheimer’sdisease(Published:22November2016)Citation:JournalofOralMicrobiology2016,8:33029-http://dx.doi.org/10.3402/jom.v8.33029