2020
CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses
Lin T, Geng T, Harrison AG, Yang D, Vella AT, Fikrig E, Wang P. CXCL10 Signaling Contributes to the Pathogenesis of Arthritogenic Alphaviruses. Viruses 2020, 12: 1252. PMID: 33147869, PMCID: PMC7692144, DOI: 10.3390/v12111252.Peer-Reviewed Original ResearchConceptsChikungunya virusAlphaviral arthritisArthritogenic alphavirusesLargest immune cell populationMacrophages/T cellsImmune cell populationsInflammatory immune responseLow viral loadWild-type miceO'nyong-nyong virusWild-type animalsRheumatic manifestationsImmune infiltratesViral loadT cellsImmune responseAlphaviral diseaseArthritic diseasesTherapeutic targetCXCL10PathogenesisViral RNACell populationsArthritisFootpad
2018
Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection
Baeza Garcia A, Siu E, Sun T, Exler V, Brito L, Hekele A, Otten G, Augustijn K, Janse CJ, Ulmer JB, Bernhagen J, Fikrig E, Geall A, Bucala R. Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Nature Communications 2018, 9: 2714. PMID: 30006528, PMCID: PMC6045615, DOI: 10.1038/s41467-018-05041-7.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdoptive TransferAnimalsAntibodies, ProtozoanCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleGene ExpressionGerminal CenterImmunologic MemoryInterferon-gammaInterleukin-12Macrophage Migration-Inhibitory FactorsMalariaMalaria VaccinesMiceMice, Inbred BALB CPlasmodium bergheiProtein IsoformsProtozoan ProteinsRNA, ProtozoanTumor Necrosis Factor-alphaVaccines, DNAConceptsCD4 T cellsT cellsBlood-stage Plasmodium infectionMemory CD4 T cellsCytokine macrophage migration inhibitory factorMacrophage migration inhibitory factorBlood-stage patencyCD8 T cellsBlood-stage infectionMigration inhibitory factorHost inflammatory responseInflammatory markers TNFGerminal center responseMIF inhibitionTfh cellsAdoptive transferIL-12Protective immunityAntibody titersMalaria infectionPlasmodium infectionInflammatory responseSporozoite infectionCenter responseHost response
2016
Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance
Acharya D, Wang P, Paul AM, Dai J, Gate D, Lowery JE, Stokic DS, Leis AA, Flavell RA, Town T, Fikrig E, Bai F. Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance. Journal Of Virology 2016, 91: 10.1128/jvi.01529-16. PMID: 27795421, PMCID: PMC5165211, DOI: 10.1128/jvi.01529-16.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytotoxicity, ImmunologicFemaleGene ExpressionHumansInterleukin-17MiceMice, Inbred C57BLNeuronsPrimary Cell CultureReceptors, Interleukin-17Recombinant ProteinsSurvival AnalysisT-Lymphocytes, CytotoxicTreatment OutcomeViral LoadVirus ReplicationWest Nile FeverWest Nile virusConceptsT cell cytotoxicityRecombinant IL-17AWest Nile virus infectionWNV-infected miceIL-17AT cellsViral burdenWNV infectionCell cytotoxicityInterleukin-17AVirus infectionMicrobial infectionsIL-17A-deficient miceT cell-mediated clearanceHigh viral burdenT-cell axisLethal WNV infectionSurvival of miceDay 6 postinfectionT cell functionWild-type miceDiverse immune functionsIL-17A.Proinflammatory cytokinesAutoimmune diseases
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
2010
TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis
Demento SL, Bonafé N, Cui W, Kaech SM, Caplan MJ, Fikrig E, Ledizet M, Fahmy TM. TLR9-Targeted Biodegradable Nanoparticles as Immunization Vectors Protect against West Nile Encephalitis. The Journal Of Immunology 2010, 185: 2989-2997. PMID: 20660705, PMCID: PMC3753007, DOI: 10.4049/jimmunol.1000768.Peer-Reviewed Original ResearchConceptsBiodegradable nanoparticlesUnmodified nanoparticlesImmune responseNanoparticlesCell-mediated immune responsesRobust humoral responseTh1 immune responseEffector T cellsAg-specific lymphocytesTh2-biased responsesAdjuvant aluminum hydroxideWest Nile encephalitisVirus encephalitisWest Nile virusAgHumoral responseCpG oligodeoxynucleotideT cellsMouse modelLive virusInfectious agentsProtein AgVaccine developmentWN virusNile virus
2009
IL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Bai F, Town T, Qian F, Wang P, Kamanaka M, Connolly TM, Gate D, Montgomery RR, Flavell RA, Fikrig E. IL-10 Signaling Blockade Controls Murine West Nile Virus Infection. PLOS Pathogens 2009, 5: e1000610. PMID: 19816558, PMCID: PMC2749443, DOI: 10.1371/journal.ppat.1000610.Peer-Reviewed Original ResearchConceptsIL-10 signalingIL-10WNV infectionWest Nile virusIL-10-deficient miceWest Nile virus infectionImportant cellular sourceSignificant human morbidityRNA flavivirusWNV pathogenesisInterleukin-10Antiviral cytokinesEtiologic rolePharmacologic blockadeDeficient miceT cellsVirus infectionPharmacologic meansTherapeutic strategiesViral infectionCellular sourceInfectionHuman morbidityNile virusMiceHuman 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
Drak2 Contributes to West Nile Virus Entry into the Brain and Lethal Encephalitis
Wang S, Welte T, McGargill M, Town T, Thompson J, Anderson JF, Flavell RA, Fikrig E, Hedrick SM, Wang T. Drak2 Contributes to West Nile Virus Entry into the Brain and Lethal Encephalitis. The Journal Of Immunology 2008, 181: 2084-2091. PMID: 18641347, PMCID: PMC2494872, DOI: 10.4049/jimmunol.181.3.2084.Peer-Reviewed Original ResearchConceptsT cellsWNV infectionIFN-gamma-producing T cellsWest Nile virus entryWNV-infected miceExperimental autoimmune encephalomyelitisLethal WNV infectionBlood-brain barrierGroups of miceDeath-associated protein familyWild-type miceAutoimmune encephalomyelitisWest Nile virusViral AgViral loadBrain barrierViral levelsLethal encephalitisPeripheral tissuesB cellsSystemic infectionMiceInfectionVirus entryBrain
2007
c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection
Pedra JH, Mattner J, Tao J, Kerfoot SM, Davis RJ, Flavell RA, Askenase PW, Yin Z, Fikrig E. c-Jun NH2-Terminal Kinase 2 Inhibits Gamma Interferon Production during Anaplasma phagocytophilum Infection. Infection And Immunity 2007, 76: 308-316. PMID: 17998313, PMCID: PMC2223674, DOI: 10.1128/iai.00599-07.Peer-Reviewed Original ResearchConceptsIFN-gamma productionA. phagocytophilum infectionPhagocytophilum infectionIFN-gammaJnk2-null miceNatural killer T cellsA. phagocytophilumKiller T cellsIFN-gamma releaseIFN-gamma secretionGamma interferon productionT cell agonistsAnaplasma phagocytophilum infectionT cellsEarly eradicationGamma interferonInterferon productionInfectionC-Jun NH2-terminal kinase-2Inhibitory effectElevated levelsMiceAnaplasma phagocytophilumPhagocytophilumKinase 2IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis
Pedra JH, Tao J, Sutterwala FS, Sukumaran B, Berliner N, Bockenstedt LK, Flavell RA, Yin Z, Fikrig E. IL-12/23p40-dependent clearance of Anaplasma phagocytophilum in the murine model of human anaplasmosis. Pathogens And Disease 2007, 50: 401-410. PMID: 17521390, DOI: 10.1111/j.1574-695x.2007.00270.x.Peer-Reviewed Original ResearchConceptsIL-12/23p40Deficient miceT cellsImmune responseHuman anaplasmosisTh1 immune responseIFN-gamma productionDay 6 postinfectionAnaplasma phagocytophilumA. phagocytophilum burdenIL-23Dendritic cellsIL-12Neutrophil numbersIFN-gammaMurine modelMicrobial agonistsPathogen clearanceDependent clearanceInfectious diseasesEarly susceptibilityPathogen eliminationCausative agentA. phagocytophilumIndependent mechanisms
2006
Cutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15
Garg R, Juncadella IJ, Ramamoorthi N, Ashish, Ananthanarayanan SK, Thomas V, Rincón M, Krueger JK, Fikrig E, Yengo CM, Anguita J. Cutting Edge: CD4 Is the Receptor for the Tick Saliva Immunosuppressor, Salp15. The Journal Of Immunology 2006, 177: 6579-6583. PMID: 17082567, PMCID: PMC4302324, DOI: 10.4049/jimmunol.177.10.6579.Peer-Reviewed Original ResearchConceptsDownstream effector proteinsSrc kinase LckC-terminal residuesLipid raft reorganizationEffector proteinsKinase LckTyrosine phosphorylationMolecular basisExtracellular domainEarly stepsSalp15T cell activationSalivary proteinsCD4 coreceptorProteinCalcium fluxCell activationT cellsCellsLckRepressionPhosphorylationIL-2 productionResiduesCoreceptorγδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice
Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, Ledizet M, Koski R, Madri JA, Barrett A, Yin Z, Craft J, Fikrig E. γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice. The Journal Of Immunology 2006, 177: 1825-1832. PMID: 16849493, DOI: 10.4049/jimmunol.177.3.1825.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesGenetic Predisposition to DiseaseImmunity, CellularImmunity, InnateImmunization, SecondaryImmunoglobulin GImmunoglobulin MImmunologic MemoryLymphocyte DepletionMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaRecurrenceT-Lymphocyte SubsetsWest Nile FeverWest Nile virusConceptsGammadelta T cellsWild-type miceT cellsWN virus infectionPrimary infectionVirus infectionWN virusNaive miceSecondary challengeImmune responseAdaptive immunityCD8 memory T cellsWest Nile virus infectionMemory T cellsProtective immune responseAdaptive immune responsesAdoptive transferWest Nile virusAb responsesLethal infectionViral challengeFatal meningoencephalitisSecondary infectionInfectionMiceGamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection
Shrestha B, Wang T, Samuel MA, Whitby K, Craft J, Fikrig E, Diamond MS. Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection. Journal Of Virology 2006, 80: 5338-5348. PMID: 16699014, PMCID: PMC1472130, DOI: 10.1128/jvi.00274-06.Peer-Reviewed Original ResearchConceptsWest Nile virusGammadelta T cellsIFN-gammaLymphoid tissueT cellsWNV infectionProtective roleSevere central nervous system infectionsCentral nervous system infectionWest Nile virus infectionGreater viral replicationNervous system infectionInfectious West Nile virusLethal WNV infectionPeripheral lymphoid tissuesIFN-gamma productionAlpha/beta interferonBone marrow reconstitution experimentsInnate immune response elementsDominant protective rolePrimary dendritic cellsAverage survival timeImmune response elementsEssential protective roleHigh viremia
2004
Immunity to West Nile virus
Wang T, Fikrig E. Immunity to West Nile virus. Current Opinion In Immunology 2004, 16: 519-523. PMID: 15245749, DOI: 10.1016/j.coi.2004.05.008.Peer-Reviewed Original ResearchConceptsWN virus infectionWest Nile virusVirus infectionImportant public health concernWN virusNile virusPublic health concernActive immunizationPassive transferEffective vaccineT cellsMurine susceptibilityHealth concernExperimental modelEnvelope proteinVirusInfectionImmunityRecent studiesImmunotherapyImmunizationPathogenesisTherapyVaccine
2003
IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection
Wang T, Scully E, Yin Z, Kim JH, Wang S, Yan J, Mamula M, Anderson JF, Craft J, Fikrig E. IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection. The Journal Of Immunology 2003, 171: 2524-2531. PMID: 12928402, DOI: 10.4049/jimmunol.171.5.2524.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsBloodCell DivisionCells, CulturedCytotoxicity, ImmunologicEncephalitis, ViralFemaleGenes, T-Cell Receptor betaGenes, T-Cell Receptor deltaGenetic Predisposition to DiseaseInterferon-gammaLymphoid TissueMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaSeverity of Illness IndexT-Lymphocyte SubsetsViral LoadWest Nile FeverWest Nile virusConceptsGammadelta T cellsWN virus infectionT cellsVirus infectionIFN-gamma-producing gammadelta T cellsWest Nile virus infectionPrevention of mortalityΓδ T cellsSplenic T cellsWild-type miceEx vivo assaysAdoptive transferWest Nile virusPerforin expressionViral loadFatal meningoencephalitisIFN-gammaMiceInfectionWN virusNile virusVivo assaysLaboratory miceCellsVirus
2002
Murine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity
Anguita J, Barthold SW, Persinski R, Hedrick MN, Huy CA, Davis RJ, Flavell RA, Fikrig E. Murine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity. The Journal Of Immunology 2002, 168: 6352-6357. PMID: 12055252, PMCID: PMC4309983, DOI: 10.4049/jimmunol.168.12.6352.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialArthritis, InfectiousBorrelia burgdorferiCD4-Positive T-LymphocytesCell LineEnzyme ActivationInflammationInterferon-gammaLyme DiseaseMAP Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhagocytesPhosphorylationProtein-Tyrosine KinasesReceptors, InterferonConceptsProinflammatory cytokine productionCytokine productionT helper type 1 responsePhagocytic cellsDevelopment of arthritisPotential new therapeutic approachType 1 responseInfection of miceExperimental murine modelMurine Lyme arthritisNew therapeutic approachesLyme arthritis developmentTreatment of inflammationCytokine burstArthritis developmentJoint inflammationLyme arthritisNF-kappa BProinflammatory cytokinesTNF-alphaT cellsMurine modelTherapeutic approachesP38 MAP kinaseSpecific Abs
1998
Borrelia burgdorferi-Infected, Interleukin-6-Deficient Mice Have Decreased Th2 Responses and Increased Lyme Arthritis
Anguita J, Rincón M, Samanta S, Barthold S, Flavell R, Fikrig E. Borrelia burgdorferi-Infected, Interleukin-6-Deficient Mice Have Decreased Th2 Responses and Increased Lyme Arthritis. The Journal Of Infectious Diseases 1998, 178: 1512-1515. PMID: 9780277, DOI: 10.1086/314448.Peer-Reviewed Original ResearchConceptsIL-6-deficient miceLyme arthritisT cellsCell responsesCD4 T cell responsesT helper cell responsesInterleukin-6-deficient miceHelper cell responsesLess IL-4CD4 T cellsEffector Th2 cellsT cell responsesBorrelia burgdorferiNaive T cellsMurine Lyme arthritisDays of infectionJoint inflammationTh2 responsesArthritis incidenceIgG2b levelsC57BL/6 miceIL-6Th2 phenotypeIL-4Th2 cells
1997
Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells.
Fikrig E, Barthold SW, Chen M, Chang CH, Flavell RA. Protective antibodies develop, and murine Lyme arthritis regresses, in the absence of MHC class II and CD4+ T cells. The Journal Of Immunology 1997, 159: 5682-6. PMID: 9548512, DOI: 10.4049/jimmunol.159.11.5682.Peer-Reviewed Original ResearchConceptsMHC class IIT cellsClass IINaive C3H/HeN miceC3H/HeN miceC57/BL6 miceCIITA-deficient miceRegression of arthritisResolution of arthritisResolution of carditisDevelopment of arthritisMurine Lyme borreliosisMHC class II transactivatorClass II moleculesClass II transactivatorIgG2b AbsProtective antibodiesBL6 miceHeN miceDeficient miceProtective AbsSCID micePersistent infectionArthritisCD4 repertoireInterleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells
Rincón M, Anguita J, Nakamura T, Fikrig E, Flavell R. Interleukin (IL)-6 Directs the Differentiation of IL-4–producing CD4+ T Cells. Journal Of Experimental Medicine 1997, 185: 461-470. PMID: 9053446, PMCID: PMC2196041, DOI: 10.1084/jem.185.3.461.Peer-Reviewed Original Research
1996
Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice.
Bockenstedt LK, Fikrig E, Barthold SW, Flavell RA, Kantor FS. Identification of a Borrelia burgdorferi OspA T cell epitope that promotes anti-OspA IgG in mice. The Journal Of Immunology 1996, 157: 5496-502. PMID: 8955199, DOI: 10.4049/jimmunol.157.12.5496.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesEpitope MappingFemaleImmunization, PassiveImmunoglobulin GInterleukin-4LipoproteinsLymphocyte ActivationMiceMice, Inbred C3HMolecular Sequence DataPeptidesT-LymphocytesVaccines, SyntheticConceptsT cell epitopesCell epitopesPhase III efficacy studiesTick-borne spirochete Borrelia burgdorferiTreatment-resistant Lyme arthritisT cell responsesSurface protein AB-cell epitopesOuter surface protein ALyme arthritisChallenge infectionIgG productionN-terminal epitopeT cellsMultisystem disorderMurine modelSpirochete Borrelia burgdorferiSubunit vaccineEfficacy studiesCell responsesRecombinant vaccineLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi