2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearance
2008
Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differencesWest Nile Virus Attenuates Activation of Primary Human Macrophages
Kong KF, Wang X, Anderson JF, Fikrig E, Montgomery RR. West Nile Virus Attenuates Activation of Primary Human Macrophages. Viral Immunology 2008, 21: 78-82. PMID: 18355125, PMCID: PMC2666911, DOI: 10.1089/vim.2007.0072.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedHumansInterferon Type IInterleukin-1betaInterleukin-8Macrophage ActivationMacrophagesSTAT1 Transcription FactorWest Nile virusConceptsWest Nile virusPrimary human macrophagesHuman macrophagesWNV infectionProduction of interleukinMosquito-borne flavivirusType I interferonProinflammatory cytokinesPotent therapyJAK/STAT pathwayIL-1betaEffective treatmentMacrophage activationI interferonRelated flavivirusesInfectionAttenuate activationNile virusMacrophagesSTAT pathwayFlavivirusesActivationDifferential responseInterleukinCytokines
2005
Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
Thomas V, Samanta S, Wu C, Berliner N, Fikrig E. Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein. Infection And Immunity 2005, 73: 208-218. PMID: 15618156, PMCID: PMC538944, DOI: 10.1128/iai.73.1.208-218.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumDNA-Binding ProteinsGene Expression RegulationHL-60 CellsHomeodomain ProteinsHumansInterferon Regulatory Factor-1Membrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNuclear ProteinsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProto-Oncogene ProteinsRepressor ProteinsSTAT1 Transcription FactorTrans-ActivatorsTranscription FactorsTranscription, GeneticConceptsCCAAT displacement proteinRegulatory factor 1IRF-1IRF-1 promoterRegulation of genesA. phagocytophilum-infected cellsFirst molecular mechanismFactor 1Interferon regulatory factor 1IFN-gamma signalingActivator proteinGene transcriptionAnaplasma phagocytophilumTranscriptional inhibitionGene expressionMolecular mechanismsNuclear extractsGamma interferon stimulationPhosphorylated STAT1Interferon stimulationGenesA. phagocytophilum infectionProteinProtein expressionReduced expression
2000
Inhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1
Diehl S, Anguita J, Hoffmeyer A, Zapton T, Ihle J, Fikrig E, Rincón M. Inhibition of Th1 Differentiation by IL-6 Is Mediated by SOCS1. Immunity 2000, 13: 805-815. PMID: 11163196, DOI: 10.1016/s1074-7613(00)00078-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCarrier ProteinsCell DifferentiationDNA-Binding ProteinsGene ExpressionInterferon-gammaInterleukin-12Interleukin-4Interleukin-6MiceReceptors, InterferonRepressor ProteinsSignal TransductionSTAT1 Transcription FactorSuppressor of Cytokine Signaling 1 ProteinSuppressor of Cytokine Signaling ProteinsTh1 CellsTrans-ActivatorsUp-RegulationConceptsIFNgamma gene expressionReceptor-mediated signalsIndependent molecular mechanismsFunctional pleiotropyTranscription 1 (STAT1) phosphorylationNovel functionNegative regulationSignal transducerGene expressionMolecular mechanismsCell differentiationCell typesT cell activationDifferentiationTh2 differentiationTh1 differentiationCell activationNonimmune cellsExpressionTh1 cell differentiationImportant roleCellsInhibitionPleiotropyPhosphorylation