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
2018
MiR-221 negatively regulates innate anti-viral response
Du H, Cui S, Li Y, Yang G, Wang P, Fikrig E, You F. MiR-221 negatively regulates innate anti-viral response. PLOS ONE 2018, 13: e0200385. PMID: 30089112, PMCID: PMC6082502, DOI: 10.1371/journal.pone.0200385.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntagomirsDNA-Binding ProteinsDown-RegulationHEK293 CellsHerpesvirus 1, HumanHumansImmunity, InnateInterferon-betaMacrophagesMiceMice, Inbred C57BLMice, KnockoutMicroRNAsPromoter Regions, GeneticProtein Serine-Threonine KinasesRhabdoviridae InfectionsTranscription FactorsVesiculovirusConceptsAntiviral responseMiR-221Innate anti-viral responseInitial antiviral responseImmune cell activationMiR-221 expressionAnti-viral responseInnate antiviral responseInnate immune systemAnti-viral defenseIFNβ productionVirus infectionMultiple candidate targetsImmune systemCell activationCandidate targetsInfectionRNA-seq analysisCritical roleDirect bindingResponseMicroRNA regulators
2016
Zika virus infection of Hofbauer cells
Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. American Journal Of Reproductive Immunology 2016, 77 PMID: 27966815, PMCID: PMC5299062, DOI: 10.1111/aji.12613.Peer-Reviewed Original ResearchConceptsCongenital Zika syndromeHofbauer cellsZika virusZIKV infectionDevelopment of CZSDengue virusSpread of ZIKVVertical transmissionFetal placental macrophagesPlacental Hofbauer cellsZika virus infectionAntenatal infectionNeonatal outcomesPlacental responsesZika syndromeVirus infectionCurrent evidenceCongenital abnormalitiesRecent studiesNeonatal developmentFetal capillariesRelated flavivirusesInfectionSpecific molecular mechanismsCertain viruses
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. pallidumIdentification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infection
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
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
A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus
Bai F, Kong KF, Dai J, Qian F, Zhang L, Brown CR, Fikrig E, Montgometry R. A Paradoxical Role for Neutrophils in the Pathogenesis of West Nile Virus. The Journal Of Infectious Diseases 2010, 202: 1804-1812. PMID: 21050124, PMCID: PMC3053000, DOI: 10.1086/657416.Peer-Reviewed Original ResearchConceptsWest Nile virusPolymorphonuclear leukocytesWNV infectionNile virusHigh viremiaViral clearanceEarly deathEarly infectionControl groupProtective roleBiphasic responseInnate immunityViral pathogenesisInfectionMiceViremiaPathogenesisParadoxical roleEfficient replicationVirusCXCL1CXCL2ChemokinesCXCR2Neutrophils
2009
Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent
Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E. Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent. Cell Host & Microbe 2009, 6: 482-492. PMID: 19917502, PMCID: PMC2843562, DOI: 10.1016/j.chom.2009.10.006.Peer-Reviewed Original ResearchConceptsArthropod-borne pathogensTick-borne BorreliaTick salivary proteinsTick proteinsB. burgdorferiLyme diseaseDisease agentsTick-borne illnessB. burgdorferi infectionLyme disease agentHuman vaccinesSalp15Infection of miceB. burgdorferi antigensMicrobial toxinsMammalian hostsBorrelia burgdorferiPathogensMechanism of actionBurgdorferi infectionProtect miceMedical importanceBurgdorferiProtective capacityMiceHuman innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionToll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E. Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity 2009, 30: 242-253. PMID: 19200759, PMCID: PMC2707901, DOI: 10.1016/j.immuni.2008.11.012.Peer-Reviewed Original ResearchConceptsToll-like receptor 7West Nile virusReceptor 7WNV infectionImmune cell infiltrationLethal WNV infectionMyeloid differentiation factorIL-23 p19IL-23 responsesIL-12 p40West Nile encephalitisIL-12 p35Infected target cellsHost defense mechanismsRNA flavivirusInnate cytokinesWNV encephalitisInterleukin-12Cell infiltrationImmune cellsTarget organsVariable severityMiceTarget cellsTissue concentrations
2008
Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differencesWest Nile Virus Attenuates Activation of Primary Human Macrophages
Kong KF, Wang X, Anderson JF, Fikrig E, Montgomery RR. West Nile Virus Attenuates Activation of Primary Human Macrophages. Viral Immunology 2008, 21: 78-82. PMID: 18355125, PMCID: PMC2666911, DOI: 10.1089/vim.2007.0072.Peer-Reviewed Original ResearchConceptsWest Nile virusPrimary human macrophagesHuman macrophagesWNV infectionProduction of interleukinMosquito-borne flavivirusType I interferonProinflammatory cytokinesPotent therapyJAK/STAT pathwayIL-1betaEffective treatmentMacrophage activationI interferonRelated flavivirusesInfectionAttenuate activationNile virusMacrophagesSTAT pathwayFlavivirusesActivationDifferential responseInterleukinCytokines
2007
West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses
Arjona A, Ledizet M, Anthony K, Bonafé N, Modis Y, Town T, Fikrig E. West Nile Virus Envelope Protein Inhibits dsRNA-Induced Innate Immune Responses. The Journal Of Immunology 2007, 179: 8403-8409. PMID: 18056386, DOI: 10.4049/jimmunol.179.12.8403.Peer-Reviewed Original ResearchConceptsWest Nile virusInnate immune responseReceptor-interacting protein 1Immune responseMajor structural proteinVirus-associated molecular patternsDipteran cellsViral replication intermediatesRNA helicasesAdaptor molecule TRIFReplication intermediatesStructural proteinsWNV envelope proteinGlycosylation patternsMolecular patternsAntiviral stateGlycosylation profileProtein 1Murine macrophagesProinflammatory cytokinesCytokine productionImmunosuppressive effectsDsRNAImmune cellsEnvelope protein
2002
Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice
Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, Medzhitov R, Fikrig E, Flavell RA. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice. Nature Medicine 2002, 8: 878-884. PMID: 12091878, DOI: 10.1038/nm732.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiCell SeparationCells, CulturedDrosophila ProteinsHumansInterleukinsLipoproteinsLyme Disease VaccinesMacrophagesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceSignal TransductionToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsToll-like receptor 1Less tumor necrosis factorTLR2-deficient miceLow antibody titersLyme disease vaccineTumor necrosis factorLow cell surface expressionOuter surface lipoproteinsVaccine recipientsAntibody titersInterleukin-6Cell surface expressionNecrosis factorOspA vaccinationDisease vaccineLow respondersInnate responseTLR2Low titersReceptor 1Substantial titersVaccinationMiceTLR1Borrelia burgdorferi