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
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
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 2
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 productionResiduesCoreceptor
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 AbsSalp15, an Ixodes scapularis Salivary Protein, Inhibits CD4+ T Cell Activation
Anguita J, Ramamoorthi N, Hovius JW, Das S, Thomas V, Persinski R, Conze D, Askenase PW, Rincón M, Kantor FS, Fikrig E. Salp15, an Ixodes scapularis Salivary Protein, Inhibits CD4+ T Cell Activation. Immunity 2002, 16: 849-859. PMID: 12121666, DOI: 10.1016/s1074-7613(02)00325-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceCalcium SignalingCD4-Positive T-LymphocytesCell DivisionDrosophilaFemaleInterleukin-2IxodesLymphocyte ActivationMiceMice, Inbred BALB CMolecular Sequence DataRabbitsRatsReceptors, Antigen, T-CellReceptors, Interleukin-2Salivary Proteins and PeptidesConceptsT cell activationVector-host interactionsI. scapularis salivaCell activationMolecular basisFunctional importanceTCR ligationSalp15ProteinSalivary proteinsTick salivaCalcium fluxIxodes scapularis salivaActivationArthropodsRepressionImmune responseLow productionPleiotropic propertiesHostInhibits CD4T cell-mediated immune responsesVivo
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
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 ResearchMeSH KeywordsAnimalsAntibodies, BacterialBorrelia burgdorferi GroupCD4-Positive T-LymphocytesCell PolarityInterleukin-6Lyme DiseaseMiceMice, Inbred C57BLMyocarditisTh2 CellsConceptsIL-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 ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCD4-Positive T-LymphocytesCell DifferentiationInterleukin-4Interleukin-6MiceMice, Inbred C57BL
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
1994
Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors
Roessner K, Russell J, Cooper S, Budd R, Fikrig E, Flavell R. Prominent T lymphocyte response to Borrelia burgdorferi from peripheral blood of unexposed donors. European Journal Of Immunology 1994, 24: 320-324. PMID: 7905415, DOI: 10.1002/eji.1830240207.Peer-Reviewed Original ResearchConceptsMemory T cellsT cellsPeripheral bloodB. burgdorferiProliferative responseNormal individualsPeripheral blood T cellsT lymphocyte responsesT cell responsesBlood T cellsNaive T cellsNormal adult peripheral bloodHLA-DR moleculesT cell clonesAdult peripheral bloodLyme disease patientsMultiple antigenic epitopesLymphocyte responsesSuperantigen responseUnexposed donorsMemory subsetsDisease patientsCord bloodLipopolysaccharide effectsCell responses