2019
Inhibition of Chikungunya Virus Replication in Primary Human Fibroblasts by Liver X Receptor Agonist
Hwang J, Wang Y, Fikrig E. Inhibition of Chikungunya Virus Replication in Primary Human Fibroblasts by Liver X Receptor Agonist. Antimicrobial Agents And Chemotherapy 2019, 63: 10.1128/aac.01220-19. PMID: 31307983, PMCID: PMC6709483, DOI: 10.1128/aac.01220-19.Peer-Reviewed Original ResearchMeSH KeywordsAntiviral AgentsApolipoproteins EATP Binding Cassette Transporter 1ATP Binding Cassette Transporter, Subfamily G, Member 1Chikungunya virusCholesterolFibroblastsGene Expression RegulationHost-Pathogen InteractionsHumansIndazolesInterferonsLiver X ReceptorsPrimary Cell CultureRNA, Small InterferingSignal TransductionVirus ReplicationConceptsChikungunya virusLiver X receptor agonistMosquito-borne chikungunya virusX receptor agonistLiver X receptorChikungunya Virus ReplicationLXR-623Acute painJoint inflammationReceptor agonistCHIKV replicationPharmacological activationSynthetic agonistsAntiviral stateVirus replicationX receptorLarge epidemicsHost factorsAgonistsPrimary human fibroblastsVirusHuman fibroblastsPainInflammationGeographic areas
2017
Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization
Narasimhan S, Schuijt TJ, Abraham NM, Rajeevan N, Coumou J, Graham M, Robson A, Wu MJ, Daffre S, Hovius JW, Fikrig E. Modulation of the tick gut milieu by a secreted tick protein favors Borrelia burgdorferi colonization. Nature Communications 2017, 8: 184. PMID: 28775250, PMCID: PMC5543126, DOI: 10.1038/s41467-017-00208-0.Peer-Reviewed Original ResearchConceptsB. burgdorferi colonizationTick gutImmune responseRNA interference-mediated silencingGut microbiomeLyme disease agentBorrelia burgdorferiB. burgdorferiGutTick proteinsVivo resultsBurgdorferiPixRAbrogationTick Ixodes scapularisArthropod vectorsDisease agentsGut proteinsIxodes scapularisAlterationsGut genesMicrobiomeTick biologyMiceBacterial biofilm formation
2015
Nlrp6 regulates intestinal antiviral innate immunity
Wang P, Zhu S, Yang L, Cui S, Pan W, Jackson R, Zheng Y, Rongvaux A, Sun Q, Yang G, Gao S, Lin R, You F, Flavell R, Fikrig E. Nlrp6 regulates intestinal antiviral innate immunity. Science 2015, 350: 826-830. PMID: 26494172, PMCID: PMC4927078, DOI: 10.1126/science.aab3145.Peer-Reviewed Original ResearchConceptsI/III interferonIntestinal antiviral innate immunityEncephalomyocarditis virusEnteric virus infectionType I/III interferonsGut microbiota homeostasisAntiviral innate immunityViral RNA sensorsViral loadControl miceVirus infectionGastrointestinal tractMicrobiota homeostasisSimilar mortalityIII interferonsAntibacterial immunityInnate immunityIntestinal tractRNA helicase DHX15MiceViral RNANLRP6Murine norovirus-1RNA sensorsMortality
2014
Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete
Narasimhan S, Rajeevan N, Liu L, Zhao YO, Heisig J, Pan J, Eppler-Epstein R, DePonte K, Fish D, Fikrig E. Gut Microbiota of the Tick Vector Ixodes scapularis Modulate Colonization of the Lyme Disease Spirochete. Cell Host & Microbe 2014, 15: 58-71. PMID: 24439898, PMCID: PMC3905459, DOI: 10.1016/j.chom.2013.12.001.Peer-Reviewed Original ResearchConceptsPeritrophic matrixTranscription factor signal transducerPathogen colonizationLyme disease spirochete Borrelia burgdorferiActivator of transcriptionGut microbiotaArthropod gutsSignal transducerLyme disease spirocheteFunctional linkArthropod vectorsMajor vectorKey glycoproteinsHuman pathogensSpirochete Borrelia burgdorferiGut epitheliumIxodes scapularis ticksColonizationGut epithelial barrierMicrobiotaExpressionGut lumenScapularis ticksBorrelia burgdorferiEpithelial barrier
2012
Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis
Liu L, Dai J, Zhao YO, Narasimhan S, Yang Y, Zhang L, Fikrig E. Ixodes scapularis JAK-STAT Pathway Regulates Tick Antimicrobial Peptides, Thereby Controlling the Agent of Human Granulocytic Anaplasmosis. The Journal Of Infectious Diseases 2012, 206: 1233-1241. PMID: 22859824, PMCID: PMC3448968, DOI: 10.1093/infdis/jis484.Peer-Reviewed Original ResearchConceptsJAK-STAT pathwayTick salivary glandsA. phagocytophilum infectionAntimicrobial peptidesElectrophoretic mobility shift assaysPeptide-encoding genesMobility shift assaysPhagocytophilum infectionHuman granulocytic anaplasmosisGene familyTransducer activatorMammalian hostsRNA interferenceShift assaysTranscription pathwayGene expressionJAK-STATJanus kinaseGranulocytic anaplasmosisSalivary glandsPathwayGenesCritical roleAnaplasma phagocytophilumKey role
2011
Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands
Liu L, Narasimhan S, Dai J, Zhang L, Cheng G, Fikrig E. Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands. EMBO Reports 2011, 12: 1196-1203. PMID: 21921936, PMCID: PMC3207102, DOI: 10.1038/embor.2011.177.Peer-Reviewed Original Research
2010
Anaplasma 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
2009
IL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Bai F, Town T, Qian F, Wang P, Kamanaka M, Connolly TM, Gate D, Montgomery RR, Flavell RA, Fikrig E. IL-10 Signaling Blockade Controls Murine West Nile Virus Infection. PLOS Pathogens 2009, 5: e1000610. PMID: 19816558, PMCID: PMC2749443, DOI: 10.1371/journal.ppat.1000610.Peer-Reviewed Original ResearchConceptsIL-10 signalingIL-10WNV infectionWest Nile virusIL-10-deficient miceWest Nile virus infectionImportant cellular sourceSignificant human morbidityRNA flavivirusWNV pathogenesisInterleukin-10Antiviral cytokinesEtiologic rolePharmacologic blockadeDeficient miceT cellsVirus infectionPharmacologic meansTherapeutic strategiesViral infectionCellular sourceInfectionHuman morbidityNile virusMiceToll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks
Fikrig E, Narasimhan S, Neelakanta G, Pal U, Chen M, Flavell R. Toll-Like Receptors 1 and 2 Heterodimers Alter Borrelia burgdorferi Gene Expression in Mice and Ticks. The Journal Of Infectious Diseases 2009, 200: 1331-1340. PMID: 19754309, PMCID: PMC2846271, DOI: 10.1086/605950.Peer-Reviewed Original ResearchConceptsGene expressionMicroarray analysisB. burgdorferi gene expressionQuantitative reverse transcription-polymerase chain reaction analysisToll-like receptor 1Reverse transcription-polymerase chain reaction analysisReceptor 1Expression profilesWild-type animalsHost TLRsArthropod vectorsMessenger RNA levelsPolymerase chain reaction analysisChain reaction analysisB. burgdorferi-infected ticksGenesBurgdorferi-infected ticksRNA levelsExpressionMurine hostBorrelia burgdorferiReaction analysisWild-type miceAnimalsHeterodimers
2007
Tick–host–pathogen interactions in Lyme borreliosis
Hovius JW, van Dam AP, Fikrig E. Tick–host–pathogen interactions in Lyme borreliosis. Trends In Parasitology 2007, 23: 434-438. PMID: 17656156, DOI: 10.1016/j.pt.2007.07.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, SurfaceArachnid VectorsBacterial VaccinesBorrelia burgdorferiGene Expression RegulationHost-Parasite InteractionsHumansIxodesLyme DiseaseReceptors, Cell SurfaceConceptsVertebrate hostsB. burgdorferi survivalB. burgdorferi genesEnzootic life cycleSpirochete survivalGene productsB. burgdorferiArthropod vectorsGenesVector moleculesLife cycleDifferent environmentsHostBorrelia burgdorferiIxodes ticksTROSPATicksSpirochetal agentBurgdorferiLyme borreliosisMicrobesSalp15ExpressionSurvivalAnaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection
Thomas V, Fikrig E. Anaplasma phagocytophilum specifically induces tyrosine phosphorylation of ROCK1 during infection. Cellular Microbiology 2007, 9: 1730-1737. PMID: 17346310, DOI: 10.1111/j.1462-5822.2007.00908.x.Peer-Reviewed Original ResearchConceptsAnaplasma phagocytophilumPSGL-1Non-antibiotic strategiesHuman granulocytic anaplasmosisA. phagocytophilum infectionA. phagocytophilum-infected cellsTick-borne agentsPolymorphonuclear leucocytesPromyelocytic cell linePhagocytophilum infectionObligate intracellular pathogensInfectionTyrosine phosphorylationIntracellular pathogensGranulocytic anaplasmosisCell linesROCK1SykPhagocytophilumPhosphorylationNeutrophilsLeucocytesAntibodies
2005
Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection
Sukumaran B, Carlyon JA, Cai JL, Berliner N, Fikrig E. Early Transcriptional Response of Human Neutrophils to Anaplasma phagocytophilum Infection. Infection And Immunity 2005, 73: 8089-8099. PMID: 16299303, PMCID: PMC1307096, DOI: 10.1128/iai.73.12.8089-8099.2005.Peer-Reviewed Original ResearchConceptsEarly transcriptional responseTranscriptional responseGene expressionHost cell gene expressionComprehensive DNA microarray analysisA. phagocytophilum infectionDNA microarray analysisObligate intracellular pathogensCell gene expressionCFLAR geneTNFSF10 geneA. phagocytophilum-infected neutrophilsCytoskeletal remodelingVesicular transportTranscriptional profilesHost pathwaysMicroarray analysisAntiapoptotic genesPromyelocytic cell lineDifferential expressionPhagocytophilum infectionHost cellsGenesHuman neutrophilsIntracellular pathogensEffects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels
Carlyon JA, Ryan D, Archer K, Fikrig E. Effects of Anaplasma phagocytophilum on Host Cell Ferritin mRNA and Protein Levels. Infection And Immunity 2005, 73: 7629-7636. PMID: 16239567, PMCID: PMC1273867, DOI: 10.1128/iai.73.11.7629-7636.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumAnimalsEhrlichiosisFerritinsGene Expression RegulationHL-60 CellsHumansMiceMice, Inbred C3HMice, SCIDNeutrophilsProtein SubunitsRNA, MessengerTime FactorsConceptsFerritin protein levelsProtein levelsHL-60 cellsA. phagocytophilumAnaplasma phagocytophilumSerum-opsonized zymosanHuman granulocytic anaplasmosisA. phagocytophilum infectionInfected HL-60 cellsTime-dependent mannerObligate intracellular bacteriumFerritin levelsInfected miceA. phagocytophilum-infected miceMajor intracellular iron storage proteinFerritin heavy chainHuman promyelocytic HL-60 cellsNADPH oxidase assemblyNeutrophilsPromyelocytic HL-60 cellsMRNA expressionPhagocytophilum infectionIntracellular pathogensGranulocytic anaplasmosisIntracellular bacteriumModulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum
Pedra JH, Sukumaran B, Carlyon JA, Berliner N, Fikrig E. Modulation of NB4 promyelocytic leukemic cell machinery by Anaplasma phagocytophilum. Genomics 2005, 86: 365-377. PMID: 16005178, DOI: 10.1016/j.ygeno.2005.05.008.Peer-Reviewed Original ResearchConceptsCell machineryA. phagocytophilum infectionTwo-dimensional differential gel electrophoresisSignal transduction genesNB4 promyelocytic leukemic cellsHigh-density oligoarraysDifferential gel electrophoresisPhagocytophilum infectionIron metabolism genesNF-kappaB genesTransduction genesObligate intracellular bacteriumApoptotic programTranscription factorsNegative obligate intracellular bacteriumCell adhesion moleculeAnaplasma phagocytophilumAntiapoptotic genesGenesIntracellular bacteriumNB4 cellsAffymetrix dataGel electrophoresisTranscriptionPromyelocytic leukemic cellsAnaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein
Thomas V, Samanta S, Wu C, Berliner N, Fikrig E. Anaplasma phagocytophilum Modulates gp91phox Gene Expression through Altered Interferon Regulatory Factor 1 and PU.1 Levels and Binding of CCAAT Displacement Protein. Infection And Immunity 2005, 73: 208-218. PMID: 15618156, PMCID: PMC538944, DOI: 10.1128/iai.73.1.208-218.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnaplasma phagocytophilumDNA-Binding ProteinsGene Expression RegulationHL-60 CellsHomeodomain ProteinsHumansInterferon Regulatory Factor-1Membrane GlycoproteinsNADPH Oxidase 2NADPH OxidasesNuclear ProteinsPhosphoproteinsPhosphorylationPromoter Regions, GeneticProto-Oncogene ProteinsRepressor ProteinsSTAT1 Transcription FactorTrans-ActivatorsTranscription FactorsTranscription, GeneticConceptsCCAAT displacement proteinRegulatory factor 1IRF-1IRF-1 promoterRegulation of genesA. phagocytophilum-infected cellsFirst molecular mechanismFactor 1Interferon regulatory factor 1IFN-gamma signalingActivator proteinGene transcriptionAnaplasma phagocytophilumTranscriptional inhibitionGene expressionMolecular mechanismsNuclear extractsGamma interferon stimulationPhosphorylated STAT1Interferon stimulationGenesA. phagocytophilum infectionProteinProtein expressionReduced expression
2004
TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi
Pal U, Li X, Wang T, Montgomery RR, Ramamoorthi N, deSilva AM, Bao F, Yang X, Pypaert M, Pradhan D, Kantor FS, Telford S, Anderson JF, Fikrig E. TROSPA, an Ixodes scapularis Receptor for Borrelia burgdorferi. Cell 2004, 119: 457-468. PMID: 15537536, DOI: 10.1016/j.cell.2004.10.027.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBase SequenceBorrelia burgdorferiCloning, MolecularGene Expression RegulationHost-Parasite InteractionsIntestinesIxodesLipoproteinsMiceMice, Inbred C3HMolecular Sequence DataReceptors, Cell SurfaceRecombinant ProteinsConceptsLyme disease agent Borrelia burgdorferiSurvival of spirochetesTick receptorMammalian hostsRNA interferenceEfficient colonizationTROSPAOuter surface protein ABorrelia burgdorferiPathogen adherencePathogen transmissionProtein AB. burgdorferi outer surface protein AMRNA levelsIxodes scapularisB. burgdorferiColonizationSurface protein AReceptorsArthropodsBurgdorferiMammalsRepressionSpirochetesTicks
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
2000
Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission
Fikrig E, Feng W, Barthold S, Telford S, Flavell R. Arthropod- and Host-Specific Borrelia burgdorferi bbk32 Expression and the Inhibition of Spirochete Transmission. The Journal Of Immunology 2000, 164: 5344-5351. PMID: 10799897, DOI: 10.4049/jimmunol.164.10.5344.Peer-Reviewed Original ResearchConceptsSpirochete transmissionLyme borreliosisB. burgdorferi infectionB. burgdorferi transmissionMechanisms of immunityIxodes scapularis ticksCutaneous sitesImmunized miceSpirochete numbersBurgdorferi infectionMurine infectionMurine hostMiceInfectionMRNA levelsScapularis ticksB. burgdorferiTick engorgementMurine tissuesVector-borne diseasesBorreliosisAdult ticksAntiserumBBK32Regulated expressionCutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox
Banerjee R, Anguita J, Roos D, Fikrig E. Cutting Edge: Infection by the Agent of Human Granulocytic Ehrlichiosis Prevents the Respiratory Burst by Down-Regulating gp91phox. The Journal Of Immunology 2000, 164: 3946-3949. PMID: 10754283, DOI: 10.4049/jimmunol.164.8.3946.Peer-Reviewed Original ResearchConceptsHGE bacteriaNADPH oxidase enzyme complexHL-60 cellsNADPH oxidaseHuman granulocytic ehrlichiosisEnzyme complexPromyelocytic cell lineTick-borne pathogensInfected cellsCell linesOrganismsMRNA levelsGp91phox proteinRT-PCRDirect inhibitionBacteriaFACS analysisPathogensMRNA expressionOxidaseGenerate superoxide anionCellsRespiratory burstSplenic neutrophilsMicrobesSALP16, a gene induced in Ixodes scapularis salivary glands during tick feeding.
Das S, Marcantonio N, Deponte K, Telford SR, Anderson JF, Kantor FS, Fikrig E. SALP16, a gene induced in Ixodes scapularis salivary glands during tick feeding. American Journal Of Tropical Medicine And Hygiene 2000, 62: 99-105. PMID: 10761732, DOI: 10.4269/ajtmh.2000.62.99.Peer-Reviewed Original ResearchAmino Acid SequenceAnimalsBase SequenceBlotting, WesternEnzyme-Linked Immunosorbent AssayFeeding BehaviorFemaleGene Expression RegulationGene LibraryGuinea PigsIxodesMiceMice, Inbred C3HMolecular Sequence DataPolymerase Chain ReactionRandom Amplified Polymorphic DNA TechniqueRecombinant ProteinsRNASalivary GlandsSalivary Proteins and PeptidesSequence Analysis, DNATick Infestations