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
2009
The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi
Hovius JW, Bijlsma MF, van der Windt GJ, Wiersinga WJ, Boukens BJ, Coumou J, Oei A, de Beer R, de Vos AF, van 't Veer C, van Dam AP, Wang P, Fikrig E, Levi MM, Roelofs JJ, van der Poll T. The Urokinase Receptor (uPAR) Facilitates Clearance of Borrelia burgdorferi. PLOS Pathogens 2009, 5: e1000447. PMID: 19461880, PMCID: PMC2678258, DOI: 10.1371/journal.ppat.1000447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, InfectiousBorrelia burgdorferiCell MovementHeartHistocytochemistryHumansLeukocytesLyme DiseaseMiceMice, Inbred C57BLMice, KnockoutMyocarditisPhagocytosisReceptors, Urokinase Plasminogen ActivatorSkinStatistics, NonparametricUp-RegulationUrinary BladderUrokinase-Type Plasminogen ActivatorConceptsB. burgdorferi numbersWT controlsPhagocytotic capacityC3H/HeN backgroundIL-1beta mRNA expressionBorrelia burgdorferiB. burgdorferi infectionRole of uPARSevere carditisBurgdorferi infectionImmune responseLeukocyte functionSpirochete Borrelia burgdorferiFibrinolytic systemPAI-1Facilitate clearanceMRNA expressionHuman leukocytesLyme borreliosisMiceB. burgdorferiCausative agentProteinase receptorUPARAdequate eradication
2006
Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosis
Hovius JW, Li X, Ramamoorthi N, Van Dam AP, Barthold SW, Van Der Poll T, Speelman P, Fikrig E. Coinfection with Borrelia burgdorferi sensu stricto and Borrelia garinii alters the course of murine Lyme borreliosis. Pathogens And Disease 2006, 49: 224-234. PMID: 17328756, DOI: 10.1111/j.1574-695x.2006.00177.x.Peer-Reviewed Original ResearchConceptsMurine Lyme borreliosisB. burgdorferi sensu strictoBurgdorferi sensu strictoLyme borreliosisBorrelia burgdorferi sensu strictoEffect of coinfectionCoinfected miceBorrelia speciesSimultaneous infectionMiceCoinfectionBorreliosisB. gariniiBorrelia gariniiReservoir hostsGariniiI. ricinus populationsSpirochetesHigher numberArthritisPreferential maintenanceInfectionPrevalenceSpirochetemia
2005
Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi
Xu Q, Seemanapalli SV, Lomax L, McShan K, Li X, Fikrig E, Liang FT. Association of Linear Plasmid 28-1 with an Arthritic Phenotype of Borrelia burgdorferi. Infection And Immunity 2005, 73: 7208-7215. PMID: 16239515, PMCID: PMC1273894, DOI: 10.1128/iai.73.11.7208-7215.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, InfectiousBorrelia burgdorferiDNA, BacterialLyme DiseaseMiceMice, SCIDPhenotypePlasmidsTransformation, BacterialConceptsSevere combined immunodeficiencyArthritic phenotypeLp28-1Linear plasmid 28Borrelia burgdorferiArthritic pathologySevere arthritisSpirochete burdenSCID miceJoint tissuesLoss of plasmidsCombined immunodeficiencyPlasmid content analysisLyme disease spirocheteInfectivity studiesPlasmid patternsDecreased infectivityVirulence factorsFurther studiesMiceBurgdorferiBacterial quantificationPathogenicity studiesTissuePhenotype
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
2000
Borrelia burgdorferi Gene Expression In Vivo and Spirochete Pathogenicity
Anguita J, Samanta S, Revilla B, Suk K, Das S, Barthold S, Fikrig E. Borrelia burgdorferi Gene Expression In Vivo and Spirochete Pathogenicity. Infection And Immunity 2000, 68: 1222-1230. PMID: 10678930, PMCID: PMC97271, DOI: 10.1128/iai.68.3.1222-1230.2000.Peer-Reviewed Original ResearchConceptsC3H/HeN miceBorrelia burgdorferi spirochetesLyme disease pathogenesisNonpathogenic spirochetesSpirochete disseminationHumoral responseImmunocompetent miceHeN miceSCID miceC3H miceImmunodeficient miceImmune serumDisease pathogenesisCarditisArthritisMiceGene expressionGenomic expression libraryDiseaseB. burgdorferiB. burgdorferi N40Borrelia burgdorferi gene expressionMammalian infectionSubsequent developmentInfection
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 burgdorferiThe 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
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 repertoireB7-1 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 responseTemporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host.
Das S, Barthold SW, Giles SS, Montgomery RR, Telford SR, Fikrig E. Temporal pattern of Borrelia burgdorferi p21 expression in ticks and the mammalian host. Journal Of Clinical Investigation 1997, 99: 987-995. PMID: 9062357, PMCID: PMC507907, DOI: 10.1172/jci119264.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceArthritis, InfectiousBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupElectrophoresis, Gel, Pulsed-FieldEnzyme-Linked Immunosorbent AssayFemaleFlagellinFluorescent Antibody Technique, IndirectGene Expression Regulation, BacterialHumansImmunizationImmunization, PassiveImmunoblottingIxodesLipoproteinsLyme DiseaseMiceMice, Inbred C3HPlasmidsPolymerase Chain ReactionRecombinant ProteinsRNA, MessengerTime FactorsConceptsInfected miceHumoral responseLate-stage Lyme diseaseMarkers of infectionCourse of diseaseMurine Lyme borreliosisB. burgdorferiB. burgdorferi infectionHuman humoral responseIxodes dammini ticksBurgdorferi-infected miceLyme arthritisActive immunizationMammalian hostsPassive transferBurgdorferi infectionC3H miceMurine infectionDay 14P21 antibodyP21 expressionLyme borreliosisLyme diseaseMiceInfection
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 persistence
1994
Target Imbalance: Disparity of Borrelia burgdorferi Genetic Material in Synovial Fluid from Lyme Arthritis Patients
Persing D, Rutledge B, Rys P, Podzorski D, Mitchell P, Ree K, Liu B, Fikrig E, Malawista S. Target Imbalance: Disparity of Borrelia burgdorferi Genetic Material in Synovial Fluid from Lyme Arthritis Patients. The Journal Of Infectious Diseases 1994, 169: 668-672. PMID: 8158048, DOI: 10.1093/infdis/169.3.668.Peer-Reviewed Original ResearchConceptsLyme arthritisClinical specimensLyme arthritis patientsUnderlying pathogenetic mechanismsPolymerase chain reaction studiesSynovial fluid specimensB. burgdorferi infectionArthritis patientsSynovial inflammationPathogenetic mechanismsBurgdorferi infectionPhysiologic imbalanceSynovial fluidFluid specimensEtiologic agentLate manifestationLyme diseaseCultured organismsBorrelia burgdorferiArthritisPatientsDNA reactivityAnalytic sensitivity