2020
An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector
Cao Y, Rosen C, Arora G, Gupta A, Booth CJ, Murfin KE, Cerny J, Lopez A, Chuang YM, Tang X, Pal U, Ring A, Narasimhan S, Fikrig E. An Ixodes scapularis Protein Disulfide Isomerase Contributes to Borrelia burgdorferi Colonization of the Vector. Infection And Immunity 2020, 88: 10.1128/iai.00426-20. PMID: 32928964, PMCID: PMC7671890, DOI: 10.1128/iai.00426-20.Peer-Reviewed Original ResearchConceptsTick gutTick bite siteVector-host interfaceAbility of spirochetesProtein disulfide isomerase A3Infected vertebrate hostsInflammatory responseBite siteLyme diseaseVertebrate hostsGutTick proteinsAdditional targetsMiceSpirochete life cycleSpirochete survivalArthropod vectorsSpirochetesRNA interferenceIllnessTicks
2015
Frostbite Protection in Mice Expressing an Antifreeze Glycoprotein
Heisig M, Mattessich S, Rembisz A, Acar A, Shapiro M, Booth CJ, Neelakanta G, Fikrig E. Frostbite Protection in Mice Expressing an Antifreeze Glycoprotein. PLOS ONE 2015, 10: e0116562. PMID: 25714402, PMCID: PMC4340617, DOI: 10.1371/journal.pone.0116562.Peer-Reviewed Original ResearchConceptsAnti-freeze glycoproteinAnti-freeze proteinsTransgenic Drosophila modelReduced cell deathDiverse speciesMammalian cellsDrosophila modelCold stressIAFGPMammalian tissuesCold shockCell deathCold hardinessDiverse mechanismsTick hostsTransgenic mouse modelPrevents tissue damagePrevention of frostbiteCold temperaturesAntifreeze glycoproteinsTransgenic miceGlycoproteinNorthern latitudesProtective functionMouse model
2013
MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum, the Agent of Syphilis
Silver AC, Dunne DW, Zeiss CJ, Bockenstedt LK, Radolf JD, Salazar JC, Fikrig E. MyD88 Deficiency Markedly Worsens Tissue Inflammation and Bacterial Clearance in Mice Infected with Treponema pallidum, the Agent of Syphilis. PLOS ONE 2013, 8: e71388. PMID: 23940747, PMCID: PMC3734110, DOI: 10.1371/journal.pone.0071388.Peer-Reviewed Original ResearchConceptsMyD88-deficient miceTreponema pallidumMyD88-deficient animalsResistance of miceToll-like receptorsWild-type miceMyD88-deficient macrophagesMacrophage-mediated clearanceHigh pathogen burdenMyD88 deficiencySpirochete Treponema pallidumWT miceTissue infiltratesBacterial clearanceExtensive inflammationTissue inflammationPlasma cellsControl animalsWT macrophagesMost TLRsAnimal modelsMixed mononuclearPathogen burdenMiceT. pallidum
2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearance
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 mechanism
2008
Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety
Yang X, Izadi H, Coleman AS, Wang P, Ma Y, Fikrig E, Anguita J, Pal U. Borrelia burgdorferi lipoprotein BmpA activates pro-inflammatory responses in human synovial cells through a protein moiety. Microbes And Infection 2008, 10: 1300-1308. PMID: 18725314, PMCID: PMC2648844, DOI: 10.1016/j.micinf.2008.07.029.Peer-Reviewed Original ResearchConceptsB mutantsWild-type B. burgdorferiP38 MAP kinase pathwayMAP kinase pathwayHuman synovial cellsSynovial cellsProtein moietyP38 MAP kinaseNF-kappaBLyme arthritisB operonKinase pathwayMAP kinaseRecombinant BmpAPro-inflammatory cytokines TNF-alphaCultured human synovial cellsLipopolysaccharide inhibitorMutantsCytokines TNF-alphaHost inflammatory responsePro-inflammatory responseCytokine responsesIL-1betaTNF-alphaInflammatory response
2007
Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis
Pal U, Wang P, Bao F, Yang X, Samanta S, Schoen R, Wormser GP, Schwartz I, Fikrig E. Borrelia burgdorferi basic membrane proteins A and B participate in the genesis of Lyme arthritis. Journal Of Experimental Medicine 2007, 205: 133-141. PMID: 18166585, PMCID: PMC2234379, DOI: 10.1084/jem.20070962.Peer-Reviewed Original ResearchConceptsLyme arthritisMouse jointsB. burgdorferi antigensBurgdorferi-infected miceSevere arthritisSpirochete numbersArthritisHost responseLyme diseaseAffinity-purified antibodiesBorrelia burgdorferiChain reactionMiceOriginal phenotypeBasic membrane proteinMutant spirochetesGene expressionJointsInflammationPathogenesisAntigenDiseaseB. burgdorferi gene expression
2004
Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis
Wang T, Town T, Alexopoulou L, Anderson JF, Fikrig E, Flavell RA. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nature Medicine 2004, 10: 1366-1373. PMID: 15558055, DOI: 10.1038/nm1140.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBlood-Brain BarrierBrainEncephalitisImmunohistochemistryInflammationMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, FluorescencePermeabilityReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 3Toll-Like ReceptorsTumor Necrosis Factor-alphaViral LoadWest Nile virusConceptsToll-like receptor 3West Nile virusWNV infectionViral loadInflammatory responseReceptor 3Blood-brain barrier compromiseTLR3-deficient miceWest Nile virus entryLethal WNV infectionBlood-brain barrierWild-type miceNeuronal injuryIntracerebroventricular administrationBrain infectionCytokine productionBrain penetrationTumor necrosisTLR3 stimulationLethal encephalitisBarrier compromiseVariable severityInfectionVirus entryNile virus
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
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