2020
Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
2015
Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers
Walker WE, Kurscheid S, Joshi S, Lopez CA, Goh G, Choi M, Barakat L, Francis J, Fisher A, Kozal M, Zapata H, Shaw A, Lifton R, Sutton RE, Fikrig E. Increased Levels of Macrophage Inflammatory Proteins Result in Resistance to R5-Tropic HIV-1 in a Subset of Elite Controllers. Journal Of Virology 2015, 89: 5502-5514. PMID: 25740989, PMCID: PMC4442529, DOI: 10.1128/jvi.00118-15.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedCase-Control StudiesCD4-Positive T-LymphocytesChemokine CCL3Chemokine CCL4Chemokine CCL5Chemokines, CCCohort StudiesFemaleGene DosageHIV InfectionsHIV Long-Term SurvivorsHIV-1Host-Pathogen InteractionsHumansMacrophage Inflammatory ProteinsMaleMiddle AgedReceptors, CCR5Receptors, CXCR4RNA, MessengerUp-RegulationConceptsElite controllersHIV-seropositive individualsAntiretroviral therapyT cellsMIP-1βMIP-1αHIV infectionSeropositive individualsAbsence of ARTR5-tropic HIV-1Macrophage inflammatory protein-1αR5-tropic HIVInflammatory protein-1αT cell resistancePandemic health problemRANTES chemokinesHIV replicationRare patientsHealthy controlsTherapeutic effectHIV entryHIV-1X4-tropicHealth problemsProtein-1α
2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cellsImmune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2013
Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infection
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
2011
Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2011, 11: 104-110. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingExtracellular Signal-Regulated MAP KinasesFemaleHumansInflammationInterleukin-8MaleMiddle AgedMonocytesMultivariate AnalysisNF-kappa BP38 Mitogen-Activated Protein KinasesPhosphorylationProtein TransportRNA, MessengerSignal TransductionToll-Like Receptor 5Tumor Necrosis Factor-alphaConceptsToll-like receptorsIL-8Multivariable mixed-effects modelsOlder individualsElevated IL-8Levels of TLR5Expression of TLR5Production of TNFAge-associated elevationAge-related decreaseDendritic cellsImmune responsivenessElderly donorsInflammatory responseImmune functionNF-κBTLR5Progressive declineMonocytesMixed effects modelsMAPK p38Significant increaseEffects modelAssociated increaseCritical mechanismImpaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus
Qian F, Wang X, Zhang L, Lin A, Zhao H, Fikrig E, Montgomery RR. Impaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus. The Journal Of Infectious Diseases 2011, 203: 1415-1424. PMID: 21398396, PMCID: PMC3080893, DOI: 10.1093/infdis/jir048.Peer-Reviewed Original ResearchConceptsDendritic cellsWest Nile virusOlder donorsAntiviral responseToll-like receptor 3Initial antiviral responseLate-phase responseNile virusSignificant age-related differencesSignificant human morbidityType I IFNQuantified cytokinesRNA flavivirusAge-related differencesYoung donorsI IFNReceptor RIGViral infectionReceptor 3Human morbidityOlder populationCritical regulatory pathwaysInterferon SignalingNuclear translocationDefective regulation
2010
Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults
Dunne DW, Shaw A, Bockenstedt LK, Allore HG, Chen S, Malawista SE, Leng L, Mizue Y, Piecychna M, Zhang L, Towle V, Bucala R, Montgomery RR, Fikrig E. Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults. PLOS ONE 2010, 5: e11343. PMID: 20596538, PMCID: PMC2893205, DOI: 10.1371/journal.pone.0011343.Peer-Reviewed Original ResearchConceptsNon-immunosuppressed adultsMIF levelsImmunosuppressive medicationsAutoimmune diseasesIL-8Cytokine productionMonocyte Toll-like receptor (TLR) expressionInnate immunityToll-like receptor expressionEnhanced innate immune responseAltered host immunityAutoimmune disease groupDownstream cytokine productionNon-immunosuppressed individualsUnderlying autoimmune diseaseFeatures of patientsHuman peripheral blood monocytesTLR4 surface expressionCytokine IL-8Number of patientsSurface expressionPeripheral blood monocytesInnate immune responseRisk of infectionImmunosuppressed adultsAge-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. The Journal Of Immunology 2010, 184: 2518-2527. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCytokinesDendritic CellsFemaleFlow CytometryHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesInterleukin-12 Subunit p40Interleukin-6Linear ModelsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionToll-Like ReceptorsTumor Necrosis Factor-alphaYoung AdultConceptsPrimary human dendritic cellsDendritic cellsHuman dendritic cellsMyeloid DCsPlasmacytoid DCsCytokine productionTLR functionTNF-alphaIntracellular cytokine productionPoor Ab responsesInfluenza vaccine responsesMyeloid dendritic cellsPlasmacytoid dendritic cellsYoung individualsIntracellular cytokine stainingIL-12 productionIFN-alpha productionTLR ligand stimulationTLR gene expressionInnate immune responseAge-Associated DecreaseTLR8 engagementInfluenza immunizationAge-associated effectsCytokine staining
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 differences
2007
Age-Associated Defect in Human TLR-1/2 Function
van Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, Allore HG, Medzhitov R, Shaw AC. Age-Associated Defect in Human TLR-1/2 Function. The Journal Of Immunology 2007, 178: 970-975. PMID: 17202359, DOI: 10.4049/jimmunol.178.2.970.Peer-Reviewed Original ResearchConceptsTLR1 surface expressionCytokine productionTLR functionTNF-alphaSurface expressionMultivariable mixed-effects modelsOlder adultsImpaired vaccine responsesTLR2 surface expressionInfection-related morbidityPeripheral blood monocytesYears of ageVaccine responsesIL-6Aged miceBlood monocytesYoung controlsFlow cytometryMixed effects modelsAge categoriesTLR1/2TLREffects modelN-palmitoylAdults
2003
An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine
Schoen RT, Deshefy-Longhi T, Van-Hoecke C, Buscarino C, Fikrig E. An open-label, nonrandomized, single-center, prospective extension, clinical trial of booster dose schedules to assess the safety profile and immunogenicity of recombinant outer-surface protein A (OspA) Lyme disease vaccine. Clinical Therapeutics 2003, 25: 210-224. PMID: 12637121, DOI: 10.1016/s0149-2918(03)90027-0.Peer-Reviewed Original ResearchConceptsLyme disease vaccineFirst booster doseSecond booster doseBooster doseAdverse eventsBooster dosesPrimary seriesMonth 24Disease vaccineClinical trialsEfficacy trialsImmune responseIncidence of AEsPattern of AEsLyme diseaseMost adverse eventsGeometric mean titersTotal IgG antibodiesProportion of subjectsPositive test resultsSeroprotective levelsBooster vaccinationMonth 36Third vaccinationDiary cards
2000
The Emergence of Another Tickborne Infection in the 12-Town Area around Lyme, Connecticut: Human Granulocytic Ehrlichiosis
IJdo J, Meek J, Cartter M, Magnarelli L, Wu C, Tenuta S, Fikrig E, Ryder R. The Emergence of Another Tickborne Infection in the 12-Town Area around Lyme, Connecticut: Human Granulocytic Ehrlichiosis. The Journal Of Infectious Diseases 2000, 181: 1388-1393. PMID: 10751139, DOI: 10.1086/315389.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisTickborne infectionProspective population-based surveillanceGranulocytic ehrlichiosisCommon tickborne infectionPopulation-based surveillancePrimary care providersSubset of seraIndirect fluorescent antibody methodIllness suggestiveCare providersLaboratory evidenceImportant causeProbable casesFluorescent antibody methodImmunoblot assayLyme diseaseInfectionAntibody methodIncidenceEhrlichiosisLymeMorbidityDiseaseSuggestive
1999
The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis
Akin E, McHugh G, Flavell R, Fikrig E, Steere A. The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis. Infection And Immunity 1999, 67: 173-181. PMID: 9864212, PMCID: PMC96293, DOI: 10.1128/iai.67.1.173-181.1999.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupChildChild, PreschoolFemaleHumansImmunoglobulin GLipoproteinsLongitudinal StudiesLyme DiseaseMaleMiddle AgedSeverity of Illness IndexConceptsAntibody responseIgG antibodiesEarly arthritisLyme arthritisIgG responsesEarly infectionDuration of arthritisChronic Lyme arthritisIgG antibody responseSerial serum samplesBorrelia burgdorferi proteinsSubsequent arthritisB. burgdorferi proteinsSurface protein CC-terminal epitopeImmune responseArthritisSubsequent severityNatural historyLyme diseasePatientsSerum samplesImmunoglobulin GProtein CInfection
1998
Differential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis
Fikrig E, Feng W, Aversa J, Schoen R, Flavell R. Differential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis. The Journal Of Infectious Diseases 1998, 178: 1198-1201. PMID: 9806060, DOI: 10.1086/515684.Peer-Reviewed Original ResearchConceptsLyme arthritisLyme diseaseHuman infectionsPhase III clinical trialsMurine Lyme borreliosisRNA polymerase chain reactionErythema migrans biopsiesErythema migransProtective immunityClinical trialsVaccine candidatesTissue specimensLyme borreliosisPatientsGene expressionBorrelia burgdorferiDiseaseFirst direct demonstrationB. burgdorferiChain reactionArthritisInfectionBorrelia burgdorferi genesOspAB. burgdorferi gene expressionVaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant
Steere A, Sikand V, Meurice F, Parenti D, Fikrig E, Schoen R, Nowakowski J, Schmid C, Laukamp S, Buscarino C, Krause D. Vaccination against Lyme Disease with Recombinant Borrelia burgdorferi Outer-Surface Lipoprotein A with Adjuvant. New England Journal Of Medicine 1998, 339: 209-215. PMID: 9673298, DOI: 10.1056/nejm199807233390401.Peer-Reviewed Original ResearchConceptsLyme diseaseSerologic testingVaccine efficacyAsymptomatic infectionLipoprotein AInjections of vaccineOuter surface lipoprotein AB. burgdorferi infectionFirst yearPlacebo recipientsPlacebo groupVaccine groupVaccine recipientsStudy entryRandomized trialsSystemic reactionsThird injectionBurgdorferi infectionEffective vaccineSkin lesionsReaction testingVaccineDefinite casesDiseaseInfectionHuman Granulocytic Ehrlichiosis During Pregnancy Treated Successfully with Rifampin
Buitrago MI, IJdo JW, Rinaudo P, Simon H, Copel J, Gadbaw J, Heimer R, Fikrig E, Bia FJ. Human Granulocytic Ehrlichiosis During Pregnancy Treated Successfully with Rifampin. Clinical Infectious Diseases 1998, 27: 213-215. PMID: 9675481, DOI: 10.1086/517678.Peer-Reviewed Case Reports and Technical Notes
1995
An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies.
Fikrig E, Liu B, Fu LL, Das S, Smallwood JI, Flavell RA, Persing DH, Schoen RT, Barthold SW, Malawista SE. An ospA frame shift, identified from DNA in Lyme arthritis synovial fluid, results in an outer surface protein A that does not bind protective antibodies. The Journal Of Immunology 1995, 155: 5700-4. PMID: 7499856, DOI: 10.4049/jimmunol.155.12.5700.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupFemaleFrameshift MutationHumansLipoproteinsLyme DiseaseMiceMice, Inbred C3HMolecular Sequence DataProtein BindingSynovial FluidConceptsSurface protein AOuter surface protein ASynovial fluidChronic Lyme arthritisSynovial fluid samplesSeparate time pointsImmune effectivenessLyme arthritisPassive immunizationProtective antibodiesHuman infectionsHuman AbsProtein ATime pointsNatural infectionInfectionBorrelia burgdorferiMiceOnly factorHuman hostFluid samplesOspAInfected hostHuman materialMicrobial persistenceSafety and Immunogenicity of an Outer Surface Protein A Vaccine in Subjects with Previous Lyme Disease
Schoen R, Meurice F, Brunet C, Cretella S, Krause D, Craft J, Fikrig E. Safety and Immunogenicity of an Outer Surface Protein A Vaccine in Subjects with Previous Lyme Disease. The Journal Of Infectious Diseases 1995, 172: 1324-1329. PMID: 7594671, DOI: 10.1093/infdis/172.5.1324.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, BacterialAntibody FormationAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferi GroupDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayHumansImmunization ScheduleImmunoglobulin GLipoproteinsLyme DiseaseProspective StudiesSafetyVaccines, SyntheticConceptsSide effectsLyme diseaseOspA vaccinePrevious Lyme diseaseThree-dose scheduleLocal side effectsSystemic side effectsLyme vaccineMild arthralgiaVaccine doseThird doseProspective studyOspA antibodiesHealthy volunteersOuter surface proteinsVaccinePatientsDiseaseImmunogenicityDoseMonthsSubjectsSurface proteinsSafetyArthralgia