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
A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe
Hovius JW, de Wever B, Sohne M, Brouwer MC, Coumou J, Wagemakers A, Oei A, Knol H, Narasimhan S, Hodiamont CJ, Jahfari S, Pals ST, Horlings HM, Fikrig E, Sprong H, van Oers MH. A case of meningoencephalitis by the relapsing fever spirochaete Borrelia miyamotoi in Europe. The Lancet 2013, 382: 658. PMID: 23953389, PMCID: PMC3987849, DOI: 10.1016/s0140-6736(13)61644-x.Peer-Reviewed Original Research
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
Age-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
2009
Human innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfection
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
1998
Human granulocytic ehrlichiosis, a tick-borne disease.
Ijdo JW, Fikrig E. Human granulocytic ehrlichiosis, a tick-borne disease. Nederlands Tijdschrift Voor Geneeskunde 1998, 142: 1778-81. PMID: 9856144.Peer-Reviewed Original ResearchConceptsPresence of leukopeniaRecent tick biteDay of admissionWhite cell countPeripheral blood smearHuman granulocytic ehrlichiosisElevated transaminasesTick-borne diseaseSevere headachePlatelet countTick biteNormal limitsCell countBlood smearsGranulocytic ehrlichiosisDays durationFull recoveryMyalgiaEhrlichiosisHeadacheWeeksLaboratory resultsLaboratory testsDurationCountVaccination 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 casesDiseaseInfectionHeat shock protein 70 of the agent of human granulocytic ehrlichiosis binds to Borrelia burgdorferi antibodies.
Ijdo J, Zhang Y, Anderson M, Goldberg D, Fikrig E. Heat shock protein 70 of the agent of human granulocytic ehrlichiosis binds to Borrelia burgdorferi antibodies. MSphere 1998, 5: 118-20. PMID: 9455892, PMCID: PMC121403, DOI: 10.1128/cdli.5.1.118-120.1998.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisEhrlichial antigenHSP-70Borrelia burgdorferi antibodiesSerologic test resultsHeat shock protein 70Shock protein 70Burgdorferi antibodiesPatient seraGranulocytic ehrlichiosisLyme diseaseFirst weekHeat shock proteinsLyme disease spirochetePrior exposureImmunoglobulin GProtein 70Immunoblot analysisAntigenShock proteinsSerumAntibodiesPatientsIllnessIgG