2020
A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis
Gupta A, Arora G, Rosen CE, Kloos Z, Cao Y, Cerny J, Sajid A, Hoornstra D, Golovchenko M, Rudenko N, Munderloh U, Hovius JW, Booth CJ, Jacobs-Wagner C, Palm NW, Ring AM, Fikrig E. A human secretome library screen reveals a role for Peptidoglycan Recognition Protein 1 in Lyme borreliosis. PLOS Pathogens 2020, 16: e1009030. PMID: 33175909, PMCID: PMC7657531, DOI: 10.1371/journal.ppat.1009030.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCytokinesGene LibraryHumansLyme DiseaseMiceMice, Inbred BALB CConceptsPeptidoglycan recognition protein 1B. burgdorferi infectionB. burgdorferiBurgdorferi infectionHost responseLow serum IgG levelsCommon vector-borne illnessDiverse host responsesSerum IgG levelsProtein 1Vector-borne illnessImmune dysregulationIgG levelsBorreliacidal activityBurgdorferi sensu latoHuman extracellular proteinsSpirochete burdenTick biteB. burgdorferi sensu latoSpirochete Borrelia burgdorferiNervous systemLyme borreliosisLyme diseaseInfectionBorrelia burgdorferi
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
2009
Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseases
2006
Antiviral Peptides Targeting the West Nile Virus Envelope Protein
Bai F, Town T, Pradhan D, Cox J, Ashish, Ledizet M, Anderson JF, Flavell RA, Krueger JK, Koski RA, Fikrig E. Antiviral Peptides Targeting the West Nile Virus Envelope Protein. Journal Of Virology 2006, 81: 2047-2055. PMID: 17151121, PMCID: PMC1797586, DOI: 10.1128/jvi.01840-06.Peer-Reviewed Original ResearchConceptsWest Nile virusMurine blood-brain barrierEnvelope proteinBlood-brain barrierPeptide 9West Nile encephalitisWNV envelope proteinCentral nervous systemWest Nile virus envelope proteinCDNA phage display libraryBrain parenchymaVirus envelope proteinHuman encephalitisViral envelope proteinsWNV infectionControl animalsPeptide-1Nervous systemRelated flavivirusesDengue virusAntiviral activityNew therapeuticsInhibition concentrationAntiviral peptidesNile virus
2005
Use of RNA Interference to Prevent Lethal Murine West Nile Virus Infection
Bai F, Wang T, Pal U, Bao F, Gould LH, Fikrig E. Use of RNA Interference to Prevent Lethal Murine West Nile Virus Infection. The Journal Of Infectious Diseases 2005, 191: 1148-1154. PMID: 15747251, DOI: 10.1086/428507.Peer-Reviewed Original ResearchConceptsWest Nile virusNile virusWest Nile virus infectionWest Nile virus replicationInjection 24 hAdministration of siRNAsIntraperitoneal inoculumViral loadProphylactic useFatal encephalitisLethal infectionVirus infectionViral infectionVirus replicationPartial protectionInfectionVirusMicePresent studyRNA interferenceEncephalitisSiRNAsAdministration
2004
Borrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses
Liang FT, Yan J, Mbow ML, Sviat SL, Gilmore RD, Mamula M, Fikrig E. Borrelia burgdorferi Changes Its Surface Antigenic Expression in Response to Host Immune Responses. Infection And Immunity 2004, 72: 5759-5767. PMID: 15385475, PMCID: PMC517580, DOI: 10.1128/iai.72.10.5759-5767.2004.Peer-Reviewed Original ResearchConceptsSurface antigenic expressionAntigenic expressionImmune attackImmune responseSevere combined immunodeficiency miceHostile immune environmentVigorous immune responseB. burgdorferiCombined immunodeficiency miceHost immune responseOspC antibodiesOuter surface protein CImmune environmentDecorin-binding protein AImmunocompetent miceImmune conditionsImmunodeficiency miceSurface protein CImmune pressureVlsE expressionLyme disease spirocheteProtein CBorrelia burgdorferiOspC expressionMammalian infectionProtective Niche for Borrelia burgdorferi to Evade Humoral Immunity
Liang FT, Brown EL, Wang T, Iozzo RV, Fikrig E. Protective Niche for Borrelia burgdorferi to Evade Humoral Immunity. American Journal Of Pathology 2004, 165: 977-985. PMID: 15331421, PMCID: PMC1618599, DOI: 10.1016/s0002-9440(10)63359-7.Peer-Reviewed Original ResearchConceptsChronic infectionHumoral immunityProtective nicheB. burgdorferiDecorin expressionLower decorin expressionDecorin-deficient miceWild-type miceStrong immune responseDecorin-binding protein ASpirochete burdenUrinary bladderImmune responsePersistent infectionMurine infectionEarly infectionInfectionExtracellular microbesDbpA expressionLyme disease spirocheteBorrelia burgdorferiC expressionTargeted disruptionBurgdorferiMiceBorrelia burgdorferi outer surface protein (osp) B expression independent of ospA
Liang FT, Caimano MJ, Radolf JD, Fikrig E. Borrelia burgdorferi outer surface protein (osp) B expression independent of ospA. Microbial Pathogenesis 2004, 37: 35-40. PMID: 15194158, DOI: 10.1016/j.micpath.2004.02.007.Peer-Reviewed Original ResearchAnimalsAntibodies, BacterialAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiDisease Models, AnimalGene Expression Regulation, BacterialLipoproteinsLyme DiseaseMiceMice, Inbred BALB CMice, SCIDPromoter Regions, GeneticRNA, BacterialRNA, MessengerTicksTranscription, Genetic
2002
Salp15, 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
Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis
Akkoyunlu M, Malawista S, Anguita J, Fikrig E. Exploitation of Interleukin-8-Induced Neutrophil Chemotaxis by the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2001, 69: 5577-5588. PMID: 11500432, PMCID: PMC98672, DOI: 10.1128/iai.69.9.5577-5588.2001.Peer-Reviewed Original ResearchConceptsHuman granulocytic ehrlichiosisInterleukin-8Granulocytic ehrlichiosisHGE bacteriaUpregulation of CXCR2IL-8 receptorsIL-8 productionIL-8 secretionSite of infectionInfected HL-60 cellsObligate intracellular bacteriumChemotaxis chamber assayNeutrophils migrateNeutrophil migrationNeutrophil chemotaxisImmunodeficient miceControl animalsBacterial disseminationHost defensePromyelocytic cell lineChamber assayIntracellular bacteriumHL-60 cellsRetinoic acidNeutrophil lineage
1993
Long-term study of cell-mediated responses to Borrelia burgdorferi in the laboratory mouse
de Souza MS, Smith AL, Beck DS, Terwilliger GA, Fikrig E, Barthold SW. Long-term study of cell-mediated responses to Borrelia burgdorferi in the laboratory mouse. Infection And Immunity 1993, 61: 1814-1822. PMID: 8478071, PMCID: PMC280770, DOI: 10.1128/iai.61.5.1814-1822.1993.Peer-Reviewed Original ResearchConceptsT cell responsesDelayed-type hypersensitivity responseVigorous T cell responseRecipient C3H miceCell-mediated responsesAntigen-specific proliferationBorrelia burgdorferi infectionB cell mitogensAntigen-specific assaysLaboratory miceAdoptive transferImmune dysfunctionHypersensitivity responseResistant miceLymphocyte proliferationLymphoid organsBurgdorferi infectionC3H miceInterleukin-2Prostaglandin productionB cellsDiminished numberLyme borreliosisImpaired proliferationLong-term studiesA monoclonal antibody to OspA inhibits association of Borrelia burgdorferi with human endothelial cells
Comstock LE, Fikrig E, Shoberg RJ, Flavell RA, Thomas DD. A monoclonal antibody to OspA inhibits association of Borrelia burgdorferi with human endothelial cells. Infection And Immunity 1993, 61: 423-431. PMID: 7678585, PMCID: PMC302746, DOI: 10.1128/iai.61.2.423-431.1993.Peer-Reviewed Original ResearchConceptsEndothelial cellsB. burgdorferiMonoclonal antibodiesInhibitory effectHUVE cellsBorrelia burgdorferiCultured human umbilical vein endothelial cellsNorth American strainsLevel of adherenceHuman umbilical vein endothelial cellsUmbilical vein endothelial cellsInhibition of adherenceImmunoglobulin G fractionVein endothelial cellsHuman endothelial cellsSurface proteinsAmerican strainsOspA epitopeOuter surface proteinsInhibitory actionPenetration assayMAbsG fractionAntibodiesBurgdorferi
1992
Nonspecific Proliferative Responses of Murine Lymphocytes to Borrelia burgdorferi Antigens
de Souza M, Fikrig E, Smith A, Flavell R, Barthold SW. Nonspecific Proliferative Responses of Murine Lymphocytes to Borrelia burgdorferi Antigens. The Journal Of Infectious Diseases 1992, 165: 471-478. PMID: 1531672, DOI: 10.1093/infdis/165.3.471.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial ProteinsBacterial VaccinesBorrelia burgdorferi GroupDose-Response Relationship, ImmunologicFlow CytometryImmunoglobulin GImmunoglobulin MLipopolysaccharidesLipoproteinsLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C3HRecombinant ProteinsSpecific Pathogen-Free OrganismsConceptsBorrelia burgdorferi antigensNaive splenocytesNonspecific proliferationProliferative responseB. burgdorferiC3H/HeNCrlBR miceRecombinant outer surface proteinB cell-enriched fractionC3H/HeJ miceNonspecific proliferative responseAntigen-specific proliferationStrains of miceCell-enriched fractionB. burgdorferi spirochetesIgG synthesisHeJ miceB cellsMitogenic effectOuter surface proteinsMurine lymphocytesLyme borreliosisMiceSplenocytesBurgdorferiAntigen