2010
Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults
Dunne DW, Shaw A, Bockenstedt LK, Allore HG, Chen S, Malawista SE, Leng L, Mizue Y, Piecychna M, Zhang L, Towle V, Bucala R, Montgomery RR, Fikrig E. Increased TLR4 Expression and Downstream Cytokine Production in Immunosuppressed Adults Compared to Non-Immunosuppressed Adults. PLOS ONE 2010, 5: e11343. PMID: 20596538, PMCID: PMC2893205, DOI: 10.1371/journal.pone.0011343.Peer-Reviewed Original ResearchConceptsNon-immunosuppressed adultsMIF levelsImmunosuppressive medicationsAutoimmune diseasesIL-8Cytokine productionMonocyte Toll-like receptor (TLR) expressionInnate immunityToll-like receptor expressionEnhanced innate immune responseAltered host immunityAutoimmune disease groupDownstream cytokine productionNon-immunosuppressed individualsUnderlying autoimmune diseaseFeatures of patientsHuman peripheral blood monocytesTLR4 surface expressionCytokine IL-8Number of patientsSurface expressionPeripheral blood monocytesInnate immune responseRisk of infectionImmunosuppressed adultsAge-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. The Journal Of Immunology 2010, 184: 2518-2527. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCytokinesDendritic CellsFemaleFlow CytometryHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesInterleukin-12 Subunit p40Interleukin-6Linear ModelsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionToll-Like ReceptorsTumor Necrosis Factor-alphaYoung AdultConceptsPrimary human dendritic cellsDendritic cellsHuman dendritic cellsMyeloid DCsPlasmacytoid DCsCytokine productionTLR functionTNF-alphaIntracellular cytokine productionPoor Ab responsesInfluenza vaccine responsesMyeloid dendritic cellsPlasmacytoid dendritic cellsYoung individualsIntracellular cytokine stainingIL-12 productionIFN-alpha productionTLR ligand stimulationTLR gene expressionInnate immune responseAge-Associated DecreaseTLR8 engagementInfluenza immunizationAge-associated effectsCytokine staining
2009
Human 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 cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfection
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 proteinAge-Associated Defect in Human TLR-1/2 Function
van Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, Allore HG, Medzhitov R, Shaw AC. Age-Associated Defect in Human TLR-1/2 Function. The Journal Of Immunology 2007, 178: 970-975. PMID: 17202359, DOI: 10.4049/jimmunol.178.2.970.Peer-Reviewed Original ResearchConceptsTLR1 surface expressionCytokine productionTLR functionTNF-alphaSurface expressionMultivariable mixed-effects modelsOlder adultsImpaired vaccine responsesTLR2 surface expressionInfection-related morbidityPeripheral blood monocytesYears of ageVaccine responsesIL-6Aged miceBlood monocytesYoung controlsFlow cytometryMixed effects modelsAge categoriesTLR1/2TLREffects modelN-palmitoylAdults
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 virus
2002
Murine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity
Anguita J, Barthold SW, Persinski R, Hedrick MN, Huy CA, Davis RJ, Flavell RA, Fikrig E. Murine Lyme Arthritis Development Mediated by p38 Mitogen-Activated Protein Kinase Activity. The Journal Of Immunology 2002, 168: 6352-6357. PMID: 12055252, PMCID: PMC4309983, DOI: 10.4049/jimmunol.168.12.6352.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialArthritis, InfectiousBorrelia burgdorferiCD4-Positive T-LymphocytesCell LineEnzyme ActivationInflammationInterferon-gammaLyme DiseaseMAP Kinase Kinase 3MAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesP38 Mitogen-Activated Protein KinasesPhagocytesPhosphorylationProtein-Tyrosine KinasesReceptors, InterferonConceptsProinflammatory cytokine productionCytokine productionT helper type 1 responsePhagocytic cellsDevelopment of arthritisPotential new therapeutic approachType 1 responseInfection of miceExperimental murine modelMurine Lyme arthritisNew therapeutic approachesLyme arthritis developmentTreatment of inflammationCytokine burstArthritis developmentJoint inflammationLyme arthritisNF-kappa BProinflammatory cytokinesTNF-alphaT cellsMurine modelTherapeutic approachesP38 MAP kinaseSpecific Abs