2020
A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus
Geng T, Lin T, Yang D, Harrison AG, Vella AT, Fikrig E, Wang P. A Critical Role for STING Signaling in Limiting Pathogenesis of Chikungunya Virus. The Journal Of Infectious Diseases 2020, 223: 2186-2196. PMID: 33161431, PMCID: PMC8205639, DOI: 10.1093/infdis/jiaa694.Peer-Reviewed Original ResearchConceptsVirus infectionSTING signalingGt miceType I IFN responseChikungunya virus infectionImmune cell infiltrationWild-type miceActivator of neutrophilsInnate immune responseExpression of interferonI IFN responseExpression of chemoattractantsRNA virus infectionDNA virus infectionInterferon genes (STING) pathwayCHIKV arthritisViremic stageArthritis progressionViral burdenArthritis pathogenesisChemokine responsesCell infiltrationJoint damageImmune responseSTING deficiencyCXCL10 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
2019
HIPK2 is necessary for type I interferon–mediated antiviral immunity
Cao L, Yang G, Gao S, Jing C, Montgomery RR, Yin Y, Wang P, Fikrig E, You F. HIPK2 is necessary for type I interferon–mediated antiviral immunity. Science Signaling 2019, 12 PMID: 30890658, PMCID: PMC6893850, DOI: 10.1126/scisignal.aau4604.Peer-Reviewed Original ResearchConceptsHomeodomain-interacting protein kinase 2Type I interferonProtein kinase 2I interferonRNA virus infectionAntiviral immunityN-terminal fragmentVesicular stomatitis virus infectionNuclear localizationActive caspasesKinase activityB transcriptionHIPK2 deficiencyKinase 2Virus infectionStomatitis virus infectionAntiviral responseWild-type miceVSV infection
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: e01529-16. 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 diseases
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
IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
Wang P, Bai F, Zenewicz LA, Dai J, Gate D, Cheng G, Yang L, Qian F, Yuan X, Montgomery RR, Flavell RA, Town T, Fikrig E. IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLOS ONE 2012, 7: e44153. PMID: 22952908, PMCID: PMC3429482, DOI: 10.1371/journal.pone.0044153.Peer-Reviewed Original ResearchConceptsWild-type miceCentral nervous systemIL-22Viral loadNeutrophil migrationType miceWest Nile virus encephalitisSimilar viral loadsLethal WNV infectionIL-22 signalingHost immune responseWNV neuroinvasionVirus encephalitisCXCR2 ligandsLeukocyte infiltrateProinflammatory cytokinesChemokine receptorsImmune responseWNV infectionViral infectionNervous systemSignaling contributesExtracellular pathogensNon-redundant roleWT leukocytes
2011
O4-S2.05 Myd-88 deficient mice show evidence of productive T pallidum infection"
Dunne D, Silver A, Fieber J, Zeiss C, Fikrig E. O4-S2.05 Myd-88 deficient mice show evidence of productive T pallidum infection". Sexually Transmitted Infections 2011, 87: a87. DOI: 10.1136/sextrans-2011-050109.149.Peer-Reviewed Original ResearchMyD-88C57BL/6 miceDeficient miceImmunohistochemical stainsImmune responseMurine modelT pallidumDay 10Intact innate immune responseOnly natural reservoirNew Zealand male rabbitsB6 control miceInnate immune cellsUseful murine modelAged C57BL/6 miceWild-type miceInnate immune responseInnate immune systemPattern recognition receptorsImmune response mechanismsDownstream cytokine responsesSyphilis infectionSystemic illnessLymph nodesCytokine responses
2010
Infectivity of Borrelia burgdorferi sensu lato is unaltered in C3-deficient mice
van Burgel ND, Balmus NC, Fikrig E, van Dam AP. Infectivity of Borrelia burgdorferi sensu lato is unaltered in C3-deficient mice. Ticks And Tick-borne Diseases 2010, 2: 20-26. PMID: 21771533, DOI: 10.1016/j.ttbdis.2010.10.003.Peer-Reviewed Original ResearchConceptsWT miceAbsence of C3B. burgdorferiB. afzeliiQuantitative PCRDifferent Borrelia speciesC3 knockout miceC3-deficient miceComplement-deficient miceWild-type miceB. afzelii infectionBorrelia burgdorferi sensu latoHuman complementInflammation scoreBurgdorferi sensu latoB. bavariensisAfzelii infectionBorrelia speciesKnockout miceMiceHeart tissueWeeksB. gariniiBurgdorferiSignificant differences
2009
Toll-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
2008
Drak2 Contributes to West Nile Virus Entry into the Brain and Lethal Encephalitis
Wang S, Welte T, McGargill M, Town T, Thompson J, Anderson JF, Flavell RA, Fikrig E, Hedrick SM, Wang T. Drak2 Contributes to West Nile Virus Entry into the Brain and Lethal Encephalitis. The Journal Of Immunology 2008, 181: 2084-2091. PMID: 18641347, PMCID: PMC2494872, DOI: 10.4049/jimmunol.181.3.2084.Peer-Reviewed Original ResearchConceptsT cellsWNV infectionIFN-gamma-producing T cellsWest Nile virus entryWNV-infected miceExperimental autoimmune encephalomyelitisLethal WNV infectionBlood-brain barrierGroups of miceDeath-associated protein familyWild-type miceAutoimmune encephalomyelitisWest Nile virusViral AgViral loadBrain barrierViral levelsLethal encephalitisPeripheral tissuesB cellsSystemic infectionMiceInfectionVirus entryBrainMatrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain▿
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain▿. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokines
2007
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion
Arjona A, Foellmer HG, Town T, Leng L, McDonald C, Wang T, Wong SJ, Montgomery RR, Fikrig E, Bucala R. Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion. Journal Of Clinical Investigation 2007, 117: 3059-3066. PMID: 17909632, PMCID: PMC1994625, DOI: 10.1172/jci32218.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorViral neuroinvasionWest Nile virusInvolvement of MIFInhibitory factorProinflammatory cytokine macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorWNV-infected miceBlood-brain barrierLife-threatening encephalitisWild-type miceAcute WNV infectionFlavivirus West Nile virusMIF expressionMIF levelsViral loadWNV encephalitisMIF actionPharmacotherapeutic approachesInflammatory responseWNV infectionCerebrospinal fluidSusceptible individualsInnate immunity
2006
γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice
Wang T, Gao Y, Scully E, Davis CT, Anderson JF, Welte T, Ledizet M, Koski R, Madri JA, Barrett A, Yin Z, Craft J, Fikrig E. γδ T Cells Facilitate Adaptive Immunity against West Nile Virus Infection in Mice. The Journal Of Immunology 2006, 177: 1825-1832. PMID: 16849493, DOI: 10.4049/jimmunol.177.3.1825.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCD8-Positive T-LymphocytesGenetic Predisposition to DiseaseImmunity, CellularImmunity, InnateImmunization, SecondaryImmunoglobulin GImmunoglobulin MImmunologic MemoryLymphocyte DepletionMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, gamma-deltaRecurrenceT-Lymphocyte SubsetsWest Nile FeverWest Nile virusConceptsGammadelta T cellsWild-type miceT cellsWN virus infectionPrimary infectionVirus infectionWN virusNaive miceSecondary challengeImmune responseAdaptive immunityCD8 memory T cellsWest Nile virus infectionMemory T cellsProtective immune responseAdaptive immune responsesAdoptive transferWest Nile virusAb responsesLethal infectionViral challengeFatal meningoencephalitisSecondary infectionInfectionMice
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 virusProtective 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 disruptionBurgdorferiMice
2003
IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection
Wang T, Scully E, Yin Z, Kim JH, Wang S, Yan J, Mamula M, Anderson JF, Craft J, Fikrig E. IFN-γ-Producing γδ T Cells Help Control Murine West Nile Virus Infection. The Journal Of Immunology 2003, 171: 2524-2531. PMID: 12928402, DOI: 10.4049/jimmunol.171.5.2524.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsBloodCell DivisionCells, CulturedCytotoxicity, ImmunologicEncephalitis, ViralFemaleGenes, T-Cell Receptor betaGenes, T-Cell Receptor deltaGenetic Predisposition to DiseaseInterferon-gammaLymphoid TissueMiceMice, Inbred C57BLMice, KnockoutReceptors, Antigen, T-Cell, alpha-betaReceptors, Antigen, T-Cell, gamma-deltaSeverity of Illness IndexT-Lymphocyte SubsetsViral LoadWest Nile FeverWest Nile virusConceptsGammadelta T cellsWN virus infectionT cellsVirus infectionIFN-gamma-producing gammadelta T cellsWest Nile virus infectionPrevention of mortalityΓδ T cellsSplenic T cellsWild-type miceEx vivo assaysAdoptive transferWest Nile virusPerforin expressionViral loadFatal meningoencephalitisIFN-gammaMiceInfectionWN virusNile virusVivo assaysLaboratory miceCellsVirusMurine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum
Carlyon JA, Akkoyunlu M, Xia L, Yago T, Wang T, Cummings RD, McEver RP, Fikrig E. Murine neutrophils require α1,3-fucosylation but not PSGL-1 for productive infection with Anaplasma phagocytophilum. Blood 2003, 102: 3387-3395. PMID: 12869507, DOI: 10.1182/blood-2003-02-0621.Peer-Reviewed Original ResearchConceptsWild-type miceP-selectin glycoprotein ligand-1Murine neutrophilsCommon tick-borne diseaseAnaplasma phagocytophilumFuc-TIVHuman granulocytic ehrlichiosisPSGL-1 expressionTick-borne diseaseNeutrophil expressionInfection burdenMurine infectionNeutrophilsGranulocytic ehrlichiosisPhagocytophilum infectionMiceHuman neutrophilsSimilar molecular featuresInfectionProductive infectionSialidase treatmentLigand 1PhagocytophilumMolecular featuresFuc-TVII