2023
Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development
Rana V, Kitsou C, Dutta S, Ronzetti M, Zhang M, Bernard Q, Smith A, Tomás-Cortázar J, Yang X, Wu M, Kepple O, Li W, Dwyer J, Matias J, Baljinnyam B, Oliver J, Rajeevan N, Pedra J, Narasimhan S, Wang Y, Munderloh U, Fikrig E, Simeonov A, Anguita J, Pal U. Dome1–JAK–STAT signaling between parasite and host integrates vector immunity and development. Science 2023, 379: eabl3837. PMID: 36634189, PMCID: PMC10122270, DOI: 10.1126/science.abl3837.Peer-Reviewed Original ResearchConceptsBlood meal acquisitionMetazoan developmentTick receptorArthropod immunityMammalian hostsSignaling pathwaysReceptor motifEvolutionary dependenceVectorial competenceStem cellsCommunication pathwaysPathwayCritical roleVector immunityHostHigh affinityGenomeAntimicrobial componentsHedgehogJAKMotifMetamorphosisImmunityParasitesPhysiology
2022
A tick C1q protein alters infectivity of the Lyme disease agent by modulating interferon γ
Tang X, Arora G, Matias J, Hart T, Cui Y, Fikrig E. A tick C1q protein alters infectivity of the Lyme disease agent by modulating interferon γ. Cell Reports 2022, 41: 111673. PMID: 36417869, PMCID: PMC9909562, DOI: 10.1016/j.celrep.2022.111673.Peer-Reviewed Original Research
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
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 2ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection
Pedra JH, Sutterwala FS, Sukumaran B, Ogura Y, Qian F, Montgomery RR, Flavell RA, Fikrig E. ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection. The Journal Of Immunology 2007, 179: 4783-4791. PMID: 17878377, DOI: 10.4049/jimmunol.179.7.4783.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnaplasmaAnaplasmosisAnimalsApoptosis Regulatory ProteinsCalcium-Binding ProteinsCaspase 1Disease SusceptibilityEnzyme ActivationHL-60 CellsHumansInterferon-gammaInterleukin-18Killer Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutPhagocytosisSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryConceptsA. phagocytophilum infectionIFN-gamma productionCaspase-1Phagocytophilum infectionIFN-gammaA. phagocytophilumIFN-gamma levelsNOD-like receptor pathwayIL-18 secretionIFN-gamma-mediated controlCentral adaptor moleculeAnaplasma phagocytophilum infectionVitro restimulationIL-18Peripheral bloodControl animalsReceptor pathwayASC deficiencyInfectionObligate intracellular pathogensIntracellular pathogensAnaplasma phagocytophilumPhagocytophilumAdaptor moleculeCritical roleIL-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
Gamma 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 ResearchMeSH KeywordsAnimalsAntiviral AgentsInterferon-gammaMiceMice, Inbred C57BLWest Nile FeverWest Nile virusConceptsWest 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
Interferon-γ deficiency reveals that 129Sv mice are inherently more susceptible to Anaplasma phagocytophilum than C57BL/6 mice
Wang T, Akkoyunlu M, Banerjee R, Fikrig E. Interferon-γ deficiency reveals that 129Sv mice are inherently more susceptible to Anaplasma phagocytophilum than C57BL/6 mice. Pathogens And Disease 2004, 42: 299-305. PMID: 15477043, DOI: 10.1016/j.femsim.2004.06.001.Peer-Reviewed Original Research
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
2001
Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination
Anguita J, Thomas V, Samanta S, Persinski R, Hernanz C, Barthold S, Fikrig E. Borrelia burgdorferi-Induced Inflammation Facilitates Spirochete Adaptation and Variable Major Protein-Like Sequence Locus Recombination. The Journal Of Immunology 2001, 167: 3383-3390. PMID: 11544329, PMCID: PMC4309988, DOI: 10.4049/jimmunol.167.6.3383.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial ProteinsBase SequenceBorrelia burgdorferiCD4-Positive T-LymphocytesDNA, BacterialGene Expression RegulationImmune SeraImmunocompetenceInflammationInterferon-gammaInterleukin-12LipoproteinsLyme DiseaseMiceMice, Inbred C3HMice, KnockoutMolecular Sequence DataReceptors, InterferonRecombination, GeneticSequence AlignmentSequence Homology, Nucleic AcidConceptsImmunocompetent miceDeficient miceB. burgdorferi N40IFN-gammaRMurine immune responseIFN-gamma-mediated responsesIFN-gamma-mediated signalsSpirochetal burdensSpirochete clearanceIL-12Immune responseIFN-gammaControl animalsDifferential immunoscreeningMice resultsMiceVariable major proteinsRT-PCRVivo adaptationB. burgdorferiClearanceBorrelia burgdorferi gene expressionB. burgdorferi survivalAdministrationVivo
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 roleCellsInhibitionPleiotropyPhosphorylationGamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia
Akkoyunlu M, Fikrig E. Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia. Infection And Immunity 2000, 68: 1827-1833. PMID: 10722570, PMCID: PMC97354, DOI: 10.1128/iai.68.4.1827-1833.2000.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteremiaConcanavalin ACytokinesDisease ProgressionDose-Response Relationship, DrugEhrlichiosisEnzyme-Linked Immunosorbent AssayFemaleHL-60 CellsHumansImmunoglobulin GInterferon-gammaMiceMice, Inbred C3HNeutrophilsReverse Transcriptase Polymerase Chain ReactionRickettsiaSpleenTime FactorsT-LymphocytesConceptsIFN-gamma-deficient miceHuman granulocytic ehrlichiosisIFN-gamma levelsDay 8Cytokine responsesIFN-gammaGamma interferonCells/HGE bacteriaGranulocytic ehrlichiosisIFN-gamma-independent mechanismMurine cytokine responsesTime pointsAgent of HGEMore IFN-gammaC3H/HeNLess interleukin-4IFN-gamma responsesMurine infection modelLater time pointsObligate intracellular bacteriumTh1 phenotypeC57BL/6 miceDNA burdenImmunocompetent mice
1999
Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists
Anguita J, Barthold S, Samanta S, Ryan J, Fikrig E. Selective Anti-Inflammatory Action of Interleukin-11 in Murine Lyme Disease: Arthritis Decreases while Carditis Persists. The Journal Of Infectious Diseases 1999, 179: 734-737. PMID: 9952389, DOI: 10.1086/314613.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAnti-Inflammatory AgentsArthritis, InfectiousFemaleHumansInflammationInterferon-gammaInterleukin-11Interleukin-12Interleukin-4Lyme DiseaseMiceMice, Inbred C3HMyocarditisNitric Oxide SynthaseNitric Oxide Synthase Type IIRecombinant ProteinsRNA, MessengerTranscription, GeneticConceptsMurine Lyme diseaseIL-11Potent anti-inflammatory propertiesInducible nitric oxide synthaseLyme diseaseMurine Lyme carditisAnti-inflammatory actionRole of interleukinAnti-inflammatory propertiesNitric oxide synthaseInnate immune responseB. burgdorferi-infected miceBurgdorferi-infected miceLyme carditisCardiac inflammationLyme arthritisIL-12Less arthritisIL-4Oxide synthaseBlocking antibodiesImmune responseControl animalsInterleukin-11Borrelia burgdorferi
1997
B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis
Anguita J, Roth R, Samanta S, Gee RJ, Barthold SW, Mamula M, Fikrig E. B7-1 and B7-2 monoclonal antibodies modulate the severity of murine Lyme arthritis. Infection And Immunity 1997, 65: 3037-3041. PMID: 9234751, PMCID: PMC175428, DOI: 10.1128/iai.65.8.3037-3041.1997.Peer-Reviewed Original ResearchConceptsLyme arthritisMurine Lyme arthritisB7-1Monoclonal antibodiesCostimulatory moleculesB7-2Immune responseInterleukin-4C3H/HeN miceB7-2 costimulatory moleculesExperimental Lyme arthritisB7-2 expressionMurine Lyme borreliosisDegree of arthritisBorrelia burgdorferi infectionSplenocyte proliferative responseDose-dependent increaseHost immune responseT cell differentiationIL-10Antibody levelsIL-12HeN miceBurgdorferi infectionProliferative response
1996
Effect of anti-interleukin 12 treatment on murine lyme borreliosis.
Anguita J, Persing DH, Rincon M, Barthold SW, Fikrig E. Effect of anti-interleukin 12 treatment on murine lyme borreliosis. Journal Of Clinical Investigation 1996, 97: 1028-1034. PMID: 8613525, PMCID: PMC507149, DOI: 10.1172/jci118494.Peer-Reviewed Original Research