2010
Age-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
2008
Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization
Hovius JW, de Jong MA, Dunnen J, Litjens M, Fikrig E, van der Poll T, Gringhuis SI, Geijtenbeek TB. Salp15 Binding to DC-SIGN Inhibits Cytokine Expression by Impairing both Nucleosome Remodeling and mRNA Stabilization. PLOS Pathogens 2008, 4: e31. PMID: 18282094, PMCID: PMC2242833, DOI: 10.1371/journal.ppat.0040031.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiCell Adhesion MoleculesCells, CulturedCytokinesDendritic CellsDose-Response Relationship, DrugHumansIxodesLectins, C-TypeNucleosomesProtein BindingProto-Oncogene Proteins c-rafReceptors, Cell SurfaceRecombinant ProteinsRNA, MessengerSalivary Proteins and PeptidesToll-Like ReceptorsConceptsRaf-1B. burgdorferi infectionSerine/threonine kinase Raf-1Mitogen-activated protein kinase kinaseKinase Raf-1Post-transcriptional levelLyme diseaseProtein kinase kinaseRaf-1 activationBurgdorferi infectionDC-SIGNTNF-alpha mRNA stabilityHuman dendritic cell functionNucleosome remodelingTick salivary proteinsDendritic cell functionKinase kinasePro-inflammatory cytokinesAdaptive immune responsesToll-like receptorsMRNA stabilityMRNA stabilizationT cell activationMolecular mechanismsMajor vector
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
The Lyme Disease Vaccine Takes Its Toll
Thomas V, Fikrig E. The Lyme Disease Vaccine Takes Its Toll. Vector-Borne And Zoonotic Diseases 2002, 2: 217-222. PMID: 12804162, DOI: 10.1089/153036602321653798.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, BacterialAntigens, SurfaceBacterial Outer Membrane ProteinsBacterial VaccinesBorrelia burgdorferiHumansLipoproteinsLyme DiseaseLyme Disease VaccinesMembrane GlycoproteinsMiceMice, KnockoutReceptors, Cell SurfaceToll-Like Receptor 1Toll-Like Receptor 2Toll-Like ReceptorsConceptsTLR2-deficient miceToll-like receptorsPathogen-associated molecular patternsOspA antibodiesSpecific Toll-like receptorsBorrelia burgdorferi outer surface proteinDetectable humoral responseMolecular patternsProtective immune responseLyme disease vaccineDistinct pathogen-associated molecular patternsVaccine recipientsHumoral responseOspA vaccineCell surface expressionOspA vaccinationImmune responseDisease vaccineInnate responseTLR2Protective responseOuter surface proteinsTLR1Lyme diseaseDevelopment of responsesHyporesponsiveness 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