2018
Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells
Silver AC, Buckley SM, Hughes ME, Hastings AK, Nitabach MN, Fikrig E. Daily oscillations in expression and responsiveness of Toll-like receptors in splenic immune cells. Heliyon 2018, 4: e00579. PMID: 29862343, PMCID: PMC5968137, DOI: 10.1016/j.heliyon.2018.e00579.Peer-Reviewed Original ResearchAdherent splenocytesToll-like receptor expressionMRNA levelsProtein levelsSplenic immune cellsToll-like receptorsDependent immune responsesZeitgeber time (ZT) 1Adherent cell populationDendritic cellsTLR3 ligandTLR ligandsCytokine expressionSplenocyte populationImmune cellsReceptor expressionImmune responseSplenic macrophagesB cellsRhythmic expressionCell populationsTLRSplenocytesDaily light-dark cycleCircadian rhythm
2014
Innate Immune Responses in the Neutrophils of Community Dwelling and Nursing Home Elders
Juthani-Mehta M, Guo X, Shaw AC, Towle V, Ning Y, Wang X, Allore HG, Fikrig E, Montgomery RR. Innate Immune Responses in the Neutrophils of Community Dwelling and Nursing Home Elders. Journal Of Aging Science 2014, 02 PMID: 25750929, PMCID: PMC4348001, DOI: 10.4172/2329-8847.1000115.Peer-Reviewed Original ResearchNursing home residentsΒ2-integrin expressionToll-like receptorsHome residentsInnate immune responseImmune responseIntegrin CD11bDisabled nursing home residentsIntegrin expressionΒ2 integrin CD11bLevels of chemokinesObservational pilot studyArea nursing homesNursing home eldersLocomotion of neutrophilsTLR4 responseChemokine inductionInfectious disease susceptibilityCommunity dwellingCommunity dwellersNursing homesEfficiency of neutrophilsNeutrophilsUnstimulated neutrophilsFlow cytometry
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
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
Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2011, 11: 104-110. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingExtracellular Signal-Regulated MAP KinasesFemaleHumansInflammationInterleukin-8MaleMiddle AgedMonocytesMultivariate AnalysisNF-kappa BP38 Mitogen-Activated Protein KinasesPhosphorylationProtein TransportRNA, MessengerSignal TransductionToll-Like Receptor 5Tumor Necrosis Factor-alphaConceptsToll-like receptorsIL-8Multivariable mixed-effects modelsOlder individualsElevated IL-8Levels of TLR5Expression of TLR5Production of TNFAge-associated elevationAge-related decreaseDendritic cellsImmune responsivenessElderly donorsInflammatory responseImmune functionNF-κBTLR5Progressive declineMonocytesMixed effects modelsMAPK p38Significant increaseEffects modelAssociated increaseCritical mechanism
2009
Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy
Demento SL, Eisenbarth SC, Foellmer HG, Platt C, Caplan MJ, Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell RA, Fahmy TM. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 2009, 27: 3013-3021. PMID: 19428913, PMCID: PMC2695996, DOI: 10.1016/j.vaccine.2009.03.034.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAnimalsAntibody FormationCarrier ProteinsCD8-Positive T-LymphocytesDendritic CellsLactic AcidLipopolysaccharidesMiceMice, Inbred C57BLNanoparticlesNLR Family, Pyrin Domain-Containing 3 ProteinPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerVaccinationViral Envelope ProteinsWest Nile FeverWest Nile Virus VaccinesConceptsPattern recognition receptorsToll-like receptorsInflammasome activationInnate immune system activationEffective adaptive immune responseIntracellular pattern recognition receptorsAntigen-presenting cellsAdaptive immune responsesWest Nile encephalitisImmune system activationInnate immune pathwaysWild-type macrophagesDendritic cellsCellular immunityVaccination approachesVaccine efficacyIL-1betaNLRP3 inflammasomeAdjuvant systemImmune responsePotent new approachMurine modelInflammasome activitySystem activationImmune pathwaysInflammasome-activating biodegradable nanoparticulates as vaccine delivery systems (135.80)
Fahmy T, DEMENTO S, Eisenbarth S, Caplan M, Saltzman W, Mellman I, Ledizet M, Fikrig E, Flavell R. Inflammasome-activating biodegradable nanoparticulates as vaccine delivery systems (135.80). The Journal Of Immunology 2009, 182: 135.80-135.80. DOI: 10.4049/jimmunol.182.supp.135.80.Peer-Reviewed Original ResearchToll-like receptorsIL-1βInflammasome activationProinflammatory cytokines IL-1βAntigen-presenting cellsClass of nanomaterialsCytokines IL-1βSurface of nanoparticlesWest Nile encephalitisInnate immune pathwaysVaccine delivery systemWild-type macrophagesCellular immunityVaccination approachesMurine modelInflammasome activityType macrophagesImmune pathwaysAdjuvant deliveryDanger signalsVaccine designModel antigenLipopolysaccharideAntigenBiocompatible polyester
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
2007
A West Nile Virus Recombinant Protein Vaccine That Coactivates Innate and Adaptive Immunity
Huleatt J, Foellmer H, Hewitt D, Tang J, Desai P, Price A, Jacobs A, Takahashi V, Huang Y, Nakaar V, Alexopoulou L, Fikrig E, Powell T, McDonald W. A West Nile Virus Recombinant Protein Vaccine That Coactivates Innate and Adaptive Immunity. The Journal Of Infectious Diseases 2007, 195: 1607-1617. PMID: 17471430, DOI: 10.1086/517613.Peer-Reviewed Original ResearchConceptsImmune responseAntibody responseImmunoglobulin G antibody responseC3H/HeN miceWest Nile virus vaccineAdaptive immune signalsTLR5-deficient miceAntigen-specific responsesG antibody responseProtective immune responseAdaptive immune responsesToll-like receptorsWNV envelope proteinLethal WNV challengeRecombinant protein vaccineInterleukin-8 productionNeutralized viral infectivityEnzyme-linked immunosorbentEffective WNV vaccinesWNV vaccineHeN miceVirus challengeProtein vaccineVirus vaccineWNV challenge
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 responses