Evidence of Microbial Translocation Associated with Perturbations in T Cell and Antigen-Presenting Cell Homeostasis in Hookworm Infections 英文参考文献.docVIP

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Evidence of Microbial Translocation Associated with Perturbations in T Cell and Antigen-Presenting Cell Homeostasis in Hookworm Infections 英文参考文献.doc

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Evidence of Microbial Translocation Associated with Perturbations in T Cell and Antigen-Presenting Cell Homeostasis in Hookworm Infections 英文参考文献

EvidenceofMicrobialTranslocationAssociatedwith PerturbationsinTCellandAntigen-PresentingCell HomeostasisinHookwormInfections PalakkalJovvianGeorge1,RajamanickamAnuradha1,NathellaPavanKumar1, VasanthapuramKumaraswami2,ThomasB.Nutman3,SubashBabu1,4* 1National Institutes of Health, International Center for Excellence in Research, Chennai, India, 2National Institute for Research in Tuberculosis, Chennai, India, 3LaboratoryofParasiticDiseases,NationalInstituteofAllergyandInfectiousDiseases,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,4SAIC- Frederick,Inc.,NCI-Frederick,Frederick,Maryland,UnitedStatesofAmerica Abstract Background: Microbial translocation (MT) is the process by which microbes or microbial products translocate from the intestinetothesystemiccirculation.MTisacommoncauseofsystemicimmuneactivationinHIVinfectionandisassociated withreducedfrequenciesofCD4 Tcells;nodataexist,however,ontheroleofMTinintestinalhelminthinfections. + Methods:WemeasuredtheplasmalevelsofMTmarkers,acute-phaseproteins,andpro-andanti-inflammatorycytokines + + inindividualswithorwithouthookworminfections.WealsoestimatedtheabsolutecountsofCD4 andCD8 Tcellsaswell asthefrequenciesofmemoryTcellanddendriticcellsubsets.Finally,wealsomeasuredthelevelsofalloftheseparameters inasubsetofindividualsfollowingtreatmentofhookworminfection. Results:OurdatasuggestthathookworminfectionischaracterizedbyincreasedlevelsofmarkersassociatedwithMTbut notacute-phaseproteinsnorpro-inflammatorycytokines.Hookworminfectionswerealsoassociatedwithincreasedlevels of the anti – inflammatory cytokine – IL-10, which was positively correlated with levels of lipopolysaccharide (LPS). In + addition,MTwasassociatedwithdecreasednumbersofCD8 Tcellsanddiminishedfrequenciesofparticulardendriticcell subsets.Antihelmintictreatmentofhookworminfectionresultedinreversalofsomeofthehematologicandmicrobiologic alterations. Conclusions:OurdataprovidecompellingevidenceforMTinahumanintestinalhelminthinfecti