2018
Host-specific expression of Ixodes scapularis salivary genes
Narasimhan S, Booth CJ, DePonte K, Wu MJ, Liang X, Mohanty S, Kantor F, Fikrig E. Host-specific expression of Ixodes scapularis salivary genes. Ticks And Tick-borne Diseases 2018, 10: 386-397. PMID: 30545615, DOI: 10.1016/j.ttbdis.2018.12.001.Peer-Reviewed Original ResearchConceptsVector-host interactionsTick infestationI. scapularisReservoir hostsNon-reservoir hostsHost-specific expressionRodent reservoir hostsInfected ticksPathogen transmissionZoonotic cycleSalivary genesIxodes scapularisTicksNatural hostScapularisInfestationTick biteLyme diseaseBorrelia burgdorferiLarval stagesPathogensHostPeromyscus leucopusStrong immune responseSalivary transcriptomeNeutralization 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
2016
Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance
Acharya D, Wang P, Paul AM, Dai J, Gate D, Lowery JE, Stokic DS, Leis AA, Flavell RA, Town T, Fikrig E, Bai F. Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance. Journal Of Virology 2016, 91: 10.1128/jvi.01529-16. PMID: 27795421, PMCID: PMC5165211, DOI: 10.1128/jvi.01529-16.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCytotoxicity, ImmunologicFemaleGene ExpressionHumansInterleukin-17MiceMice, Inbred C57BLNeuronsPrimary Cell CultureReceptors, Interleukin-17Recombinant ProteinsSurvival AnalysisT-Lymphocytes, CytotoxicTreatment OutcomeViral LoadVirus ReplicationWest Nile FeverWest Nile virusConceptsT cell cytotoxicityRecombinant IL-17AWest Nile virus infectionWNV-infected miceIL-17AT cellsViral burdenWNV infectionCell cytotoxicityInterleukin-17AVirus infectionMicrobial infectionsIL-17A-deficient miceT cell-mediated clearanceHigh viral burdenT-cell axisLethal WNV infectionSurvival of miceDay 6 postinfectionT cell functionWild-type miceDiverse immune functionsIL-17A.Proinflammatory cytokinesAutoimmune diseasesA novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection
Troupin A, Londono-Renteria B, Conway MJ, Cloherty E, Jameson S, Higgs S, Vanlandingham DL, Fikrig E, Colpitts TM. A novel mosquito ubiquitin targets viral envelope protein for degradation and reduces virion production during dengue virus infection. Biochimica Et Biophysica Acta 2016, 1860: 1898-1909. PMID: 27241849, PMCID: PMC4949077, DOI: 10.1016/j.bbagen.2016.05.033.Peer-Reviewed Original ResearchConceptsProtein degradationUbiquitin proteinGene expressionProtein expression constructsSite-directed mutagenesisViral protein degradationInnate immune signalingDengue virusProteasomal degradationProtein interactionsExpression constructsMosquito cellsSignificant human diseaseMicroarray analysisImmune signalingViral envelope proteinsVirus infectionHuman diseasesBlood feedingAmino acidsProteinMultiple functionsQRT-PCRVirion productionAntiviral function
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 ResearchMeSH KeywordsAnimalsAntifreeze ProteinsCell SurvivalCold TemperatureFibroblastsFrostbiteGene ExpressionInflammationMiceMice, TransgenicConceptsAnti-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
2014
Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes
Li MW, Wang J, Zhao YO, Fikrig E. Innexin AGAP001476 Is Critical for Mediating Anti-Plasmodium Responses in Anopheles Mosquitoes. Journal Of Biological Chemistry 2014, 289: 24885-24897. PMID: 25035430, PMCID: PMC4155657, DOI: 10.1074/jbc.m114.554519.Peer-Reviewed Original ResearchConceptsAnti-Plasmodium responseToll pathwayInnate immune responseGap junction proteinIMD pathwaySignal transductionExtracellular communicationSimultaneous knockdownAnopheles gambiaeImmune responseMidgut epitheliumInhibitor studiesKnockdownPlasmodium falciparum infectionCactusBlood mealGap junctionsVitellogenin levelsOocyst numbersAnopheles mosquitoesJunction proteinsCritical rolePathwayMRNA levelsMosquitoes
2013
Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis
Narasimhan S, Perez O, Mootien S, DePonte K, Koski RA, Fikrig E, Ledizet M. Characterization of Ixophilin, A Thrombin Inhibitor from the Gut of Ixodes scapularis. PLOS ONE 2013, 8: e68012. PMID: 23874485, PMCID: PMC3706618, DOI: 10.1371/journal.pone.0068012.Peer-Reviewed Original ResearchConceptsTick gutBlood mealVertebrate hostsTick gut proteinsPathogen transmissionBorrelia burgdorferi transmissionAnticoagulation strategiesThrombin inhibitory activityHemostatic mechanismThrombin inhibitorsMammalian coagulationIxodes scapularisMammalian hostsTick salivaLyme diseaseKey enzymeGut proteinsBorrelia burgdorferiTick feedingHost bloodHours of feedingGutFunctional suiteTick proteinsHuman pathogens
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 clearanceThe Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity
Silver AC, Arjona A, Walker WE, Fikrig E. The Circadian Clock Controls Toll-like Receptor 9-Mediated Innate and Adaptive Immunity. Immunity 2012, 36: 251-261. PMID: 22342842, PMCID: PMC3315694, DOI: 10.1016/j.immuni.2011.12.017.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Receptor 9Adaptive immune responsesInnate immune systemCircadian molecular clockSepsis inductionTLR9 expressionTLR9 ligandsImmune responseVaccination modelAdaptive immunityMouse modelImmune systemDisease severityHomeostatic processesCircadian rhythmBiologic processesDirect molecular linkMolecular linkRhythmSepsisImmunotherapyImmunoprophylaxisExpressionInnate
2011
Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells
Silver AC, Arjona A, Hughes ME, Nitabach MN, Fikrig E. Circadian expression of clock genes in mouse macrophages, dendritic cells, and B cells. Brain Behavior And Immunity 2011, 26: 407-413. PMID: 22019350, PMCID: PMC3336152, DOI: 10.1016/j.bbi.2011.10.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsARNTL Transcription FactorsB-LymphocytesCircadian RhythmCircadian Rhythm Signaling Peptides and ProteinsCLOCK ProteinsDendritic CellsDNA-Binding ProteinsGene ExpressionMacrophagesMiceNuclear Receptor Subfamily 1, Group D, Member 1Period Circadian ProteinsPhotoperiodSpleenTranscription FactorsConceptsMolecular clock mechanismClock genesClock mechanismGene expressionClock-controlled transcription factorsFunctional molecular clockAspects of physiologyConstant environmental conditionsMolecular clockTranscription factorsCircadian expressionB cellsEnvironmental conditionsLight-dark cycleMouse macrophagesDaily rhythmsGenesExpressionCellsDendritic cellsMurine spleenMammalsMacrophagesSplenic NK cellsImmune cells
2010
Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum
Pedra JH, Narasimhan S, Rendić D, DePonte K, Bell‐Sakyi L, Wilson IB, Fikrig E. Fucosylation enhances colonization of ticks by Anaplasma phagocytophilum. Cellular Microbiology 2010, 12: 1222-1234. PMID: 20331643, PMCID: PMC3250644, DOI: 10.1111/j.1462-5822.2010.01464.x.Peer-Reviewed Original ResearchConceptsA. phagocytophilumAnaplasma phagocytophilumHuman granulocytic anaplasmosisBacterium Anaplasma phagocytophilumGranulocytic anaplasmosisPathological processesTick feedingPhagocytophilumMicrobial pathogenesisNovel mechanismPathogen colonizationTick cellsFucosylated structuresTicksPathogen invasionPathogenesisAnaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2006
Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisition.
Pedra JH, Narasimhan S, Deponte K, Marcantonio N, Kantor FS, Fikrig E. Disruption of the salivary protein 14 in Ixodes scapularis nymphs and impact on pathogen acquisition. American Journal Of Tropical Medicine And Hygiene 2006, 75: 677-82. PMID: 17038693, DOI: 10.4269/ajtmh.2006.75.677.Peer-Reviewed Original ResearchConceptsScapularis nymphsProtein 14Adult Ixodes scapularisIxodes scapularis nymphsI. scapularisBorrelia burgdorferiTick feedingI. scapularis nymphsB. burgdorferiFamily expressionEngorgement weightTick weightPhysiological rolePathogen acquisitionBurgdorferiIxodes scapularisRNA interferenceExpressionDifferent mechanismsFeedingScapularis
2002
Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis
IJdo JW, Wu C, Telford SR, Fikrig E. Differential Expression of the p44 Gene Family in the Agent of Human Granulocytic Ehrlichiosis. Infection And Immunity 2002, 70: 5295-5298. PMID: 12183586, PMCID: PMC128253, DOI: 10.1128/iai.70.9.5295-5298.2002.Peer-Reviewed Original ResearchConceptsP44 geneDifferential expressionHuman granulocytic ehrlichiosisGene familyAntigenic variationHGE bacteriaTransmission feedingGranulocytic ehrlichiosisGenesHypervariable regionInfected C3H miceP44 expressionTick transmissionExpressionSCID miceC3H miceHGE infectionMurine modelInfected ticksSalivary glandsNymphal ticksMiceTicksEhrlichiosisBacteriaExamination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding
Narasimhan S, Santiago F, Koski RA, Brei B, Anderson JF, Fish D, Fikrig E. Examination of the Borrelia burgdorferi Transcriptome in Ixodes scapularis during Feeding. Journal Of Bacteriology 2002, 184: 3122-3125. PMID: 12003955, PMCID: PMC135063, DOI: 10.1128/jb.184.11.3122-3125.2002.Peer-Reviewed Original ResearchConceptsBorrelia burgdorferi gene expressionB. burgdorferi genesPeriplasmic proteinsSignal transductionChromosomal genesPutative lipoproteinSubstrate transportGene expressionDifferential expressionGenesEnergy metabolismIxodes scapularis ticksGlobal analysisIxodes scapularisScapularis ticksExpressionTranscriptomeTransductionTicksProteinFeedingMetabolismScapularis
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 roleCellsInhibitionPleiotropyPhosphorylationBorrelia 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
Borrelia burgdorferi erpT expression in the arthropod vector and murine host
Fikrig E, Chen M, Barthold S, Anguita J, Feng W, Telford S, Flavell R. Borrelia burgdorferi erpT expression in the arthropod vector and murine host. Molecular Microbiology 1999, 31: 281-290. PMID: 9987129, DOI: 10.1046/j.1365-2958.1999.01171.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArachnid VectorsBacterial ProteinsBorrelia burgdorferi GroupFemaleGene ExpressionMiceMice, Inbred C3HTicksConceptsRNA polymerase chain reactionPolymerase chain reactionB. burgdorferi-infected miceBurgdorferi-infected miceB. burgdorferiMurine infectionChain reactionMurine hostImmunization of miceExtracutaneous sitesDifferential antibodyPersistent infectionArthropod vectorsIndirect immunofluorescenceBSK II mediumMiceImmunofluorescence studiesInfectionBurgdorferiAntibodiesAntigenBorrelia burgdorferi genesSmall minorityMammalian hostsNorthern blot
1998
Differential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis
Fikrig E, Feng W, Aversa J, Schoen R, Flavell R. Differential Expression of Borrelia burgdorferi Genes during Erythema Migrans and Lyme Arthritis. The Journal Of Infectious Diseases 1998, 178: 1198-1201. PMID: 9806060, DOI: 10.1086/515684.Peer-Reviewed Original ResearchConceptsLyme arthritisLyme diseaseHuman infectionsPhase III clinical trialsMurine Lyme borreliosisRNA polymerase chain reactionErythema migrans biopsiesErythema migransProtective immunityClinical trialsVaccine candidatesTissue specimensLyme borreliosisPatientsGene expressionBorrelia burgdorferiDiseaseFirst direct demonstrationB. burgdorferiChain reactionArthritisInfectionBorrelia burgdorferi genesOspAB. burgdorferi gene expression
1995
Borrelia burgdorferi genes selectively expressed in the infected host.
Suk K, Das S, Sun W, Jwang B, Barthold SW, Flavell RA, Fikrig E. Borrelia burgdorferi genes selectively expressed in the infected host. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 4269-4273. PMID: 7753795, PMCID: PMC41925, DOI: 10.1073/pnas.92.10.4269.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigen-Antibody ReactionsAntigens, BacterialBacterial VaccinesBase SequenceBlotting, NorthernBorrelia burgdorferi GroupDNA PrimersDNA, BacterialGene ExpressionGene Transfer TechniquesGenes, BacterialGenomic LibraryImmunizationMiceMice, Inbred C3HMolecular Sequence DataPolymerase Chain ReactionSequence Homology, Amino AcidConceptsInfected hostRNA PCRDifferential screeningScreening strategyExpression libraryB. burgdorferiSelective expressionNorthern blot analysisBlot analysisMiceBorrelia burgdorferi genesB. burgdorferi genesVivoGene transfer systemMicrobial genesScreening methodPathogenic microorganismsScreeningGenesAntigen