Association of Neisseria gonorrhoeae OpaCEA with Dendritic Cells Suppresses Their Ability to Elicit an HIV-1-Specific T Cell Memory Response.docVIP
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Association of Neisseria gonorrhoeae OpaCEA with Dendritic Cells Suppresses Their Ability to Elicit an HIV-1-Specific T Cell Memory Response
AssociationofNeisseriagonorrhoeaeOpaCEA with
DendriticCellsSuppressesTheirAbilitytoElicitanHIV-1-
SpecificTCellMemoryResponse
QiguiYu1*,EdithM.C.Chow2,ShannonE.McCaw2,NingjieHu1,DanielByrd1,TohtiAmet1,SishunHu1,
MarioA.Ostrowski,ScottD.Gray-Owen2*
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America, 2Department of Molecular
Genetics,and3ClinicalSciencesDivision,UniversityofToronto,Toronto,Ontario,Canada
Abstract
Infection with Neisseria gonorrhoeae (N. gonorrhoeae) can trigger an intense local inflammatory response at the site of
infection,yetthereislittlespecificimmuneresponseordevelopmentofimmunememory.Gonococcalsurfaceepitopesare
knowntoundergoantigenicvariation;however,thisisunlikelytoexplaintheweakimmuneresponsetoinfectionsince
individualscanbere-infectedbythesameserotype.Previousstudieshavedemonstratedthatthecolonyopacity-associated
(Opa)proteinsontheN.gonorrhoeaesurfacecanbindhumancarcinoembryonicantigen-relatedcellularadhesionmolecule
+
1 (CEACAM1) on CD4 T cells to suppress T cell activation and proliferation. Interesting in this regard, N. gonorrhoeae
infectionisassociatedwithimpairedHIV-1(humanimmunodeficiencyvirustype1)-specificcytotoxicT-lymphocyte(CTL)
responsesandwithtransientincreasesinplasmaviremiainHIV-1-infectedpatients,suggestingthatN.gonorrhoeaemay
alsosubvertimmuneresponsestoco-pathogens.Sincedendriticcells(DCs)areprofessionalantigenpresentingcells(APCs)
thatplayakeyroleintheinductionofanadaptiveimmuneresponse,weinvestigatedtheeffectsofN.gonorrhoeaeOpa
proteinsonhumanDCactivationandfunction.WhilemorphologicalchangesreminiscentofDCmaturationwereevident
uponN.gonorrhoeaeinfection,weobservedamarkeddownregulationofDCmaturationmarkerCD83whenthegonococci
expressing CEACAM1-specific OpaCEA, but not other Opa variants. Consistent with a gonococcal-induced defect in
maturation,OpaCEAbindingtoCEACAM1reducedtheDCs’capacitytostimulateanallogeneicTcellproliferativeresponse.
M
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