2003
Toll-like receptors and their role in experimental models of microbial infection
Qureshi S, Medzhitov R. Toll-like receptors and their role in experimental models of microbial infection. Genes & Immunity 2003, 4: 87-94. PMID: 12618855, DOI: 10.1038/sj.gene.6363937.Peer-Reviewed Original ResearchConceptsImmune systemHost defenseToll-like receptor (TLR) familyExperimental modelTLR-deficient miceMicrobial infectionsAdaptive immune responsesToll-like receptorsEffective host defenseLimited human studiesInnate immune systemAdaptive immune systemPrompt recognitionImmune responseHuman studiesInnate immunityInfectious threatsInfectionReceptor familyAntimicrobial effectorsContainment measuresPathogen recognitionConstant surveillancePathogensActivation
2002
Toll-Like Receptors and Their Ligands
Barton G, Medzhitov R. Toll-Like Receptors and Their Ligands. Current Topics In Microbiology And Immunology 2002, 270: 81-92. PMID: 12467245, DOI: 10.1007/978-3-642-59430-4_5.Peer-Reviewed Original Research
2001
Evolutionary perspective on innate immune recognition
Mushegian A, Medzhitov R. Evolutionary perspective on innate immune recognition. Journal Of Cell Biology 2001, 155: 705-710. PMID: 11724812, PMCID: PMC2150873, DOI: 10.1083/jcb.200107040.Peer-Reviewed Original ResearchDrosophila MyD88 is an adapter in the Toll signaling pathway
Horng T, Medzhitov R. Drosophila MyD88 is an adapter in the Toll signaling pathway. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 12654-12658. PMID: 11606776, PMCID: PMC60109, DOI: 10.1073/pnas.231471798.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationApoptosisCarrier ProteinsCaspasesDrosophila ProteinsFas-Associated Death Domain ProteinInsect ProteinsMembrane GlycoproteinsMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicToll-Like ReceptorsConceptsCell surface receptorsToll-1Death domain-containing proteinDomain-containing proteinsSurface receptorsDominant-negative versionDeath receptor-mediated pathwayDrosophila homologueS2 cellsApical caspasesEvolutionary ancestorInvertebrate cellsDMyD88Toll receptorAdult fliesDownstream componentsCaspase activationHuman MyD88Reporter geneInnate immune recognitionGenetic studiesAntifungal peptidesReceptor-mediated pathwayApoptosis inductionPelleRecognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou L, Holt A, Medzhitov R, Flavell R. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 2001, 413: 732-738. PMID: 11607032, DOI: 10.1038/35099560.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsAntigens, DifferentiationB-LymphocytesCell LineCells, CulturedCytokinesDrosophila ProteinsGalactosamineHumansInterferon Type ILymphocyte ActivationMacrophagesMembrane GlycoproteinsMiceMitogen-Activated Protein KinasesMolecular Sequence DataMyeloid Differentiation Factor 88NF-kappa BPoly I-CReceptors, Cell SurfaceReceptors, ImmunologicRNA, Double-StrandedSequence Homology, Amino AcidSignal TransductionToll-Like Receptor 3Toll-Like ReceptorsVirus DiseasesConceptsToll-like receptorsNF-κBI interferonInnate immune recognition receptorsToll-like receptor 3TLR3-deficient miceMolecular patternsPolyinosine-polycytidylic acidMitogen-activated proteinType I interferonMammalian TLR3Dendritic cellsInflammatory cytokinesImmune recognition receptorsViral infectionD-galactosamineReceptor 3MyD88Reduced productionReceptorsActivationMicrobial pathogensLethal effectsMost virusesAdaptor proteinTIRAP: an adapter molecule in the Toll signaling pathway
Horng T, Barton G, Medzhitov R. TIRAP: an adapter molecule in the Toll signaling pathway. Nature Immunology 2001, 2: 835-841. PMID: 11526399, DOI: 10.1038/ni0901-835.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsAntigens, DifferentiationCell DifferentiationCell LineCloning, MolecularCpG IslandsDendritic CellsDrosophila ProteinsEIF-2 KinaseHSP40 Heat-Shock ProteinsHumansLipopolysaccharidesMembrane GlycoproteinsMiceMolecular Sequence DataMutationMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicReceptors, Interleukin-1Sequence Homology, Amino AcidSignal TransductionToll-Like Receptor 4Toll-Like Receptor 9Toll-Like ReceptorsConceptsMammalian Toll-like receptorsProtein kinase PKRMitogen-activated protein kinaseToll-like receptorsKinase PKRAdapter proteinProtein kinaseMyD88-independent signalingPathways downstreamAdapter moleculeNF-κBSignaling pathwaysCellular responsesMicrobial metabolismAdapter protein MyD88MyD88-dependent signaling pathwaysProtein MyD88Absence of MyD88MyD88-deficient miceDendritic cell maturationCell maturationPathwayTLR4 ligationKinasePKR
2000
Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley J, Tong L. Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 2000, 408: 111-115. PMID: 11081518, DOI: 10.1038/35040600.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCloning, MolecularCrystallography, X-RayDrosophilaDrosophila ProteinsHumansMembrane GlycoproteinsMiceModels, MolecularMolecular Sequence DataPoint MutationProtein BindingProtein ConformationProtein Structure, TertiaryReceptors, Cell SurfaceReceptors, Interleukin-1Recombinant Fusion ProteinsStructure-Activity RelationshipToll-Like Receptor 1Toll-Like Receptor 2Toll-Like Receptor 4Toll-Like ReceptorsConceptsTIR domainSignal transductionFunctional studiesToll/interleukinSingle point mutationToll-like receptorsEquivalent residuesStructural basisReceptor domainInterleukin-1 receptorHuman TLR1Receptor signalingMutationsMyD88 adapterTransductionMurine TLR4Host immune responseAdaptive immunitySurface patchesResiduesReceptorsDomainMutantsMutagenesisYeastThe Toll receptor family and microbial recognition
Medzhitov R, Janeway C. The Toll receptor family and microbial recognition. Trends In Microbiology 2000, 8: 452-456. PMID: 11044679, DOI: 10.1016/s0966-842x(00)01845-x.Peer-Reviewed Original ResearchViral interference with IL-1 and Toll signaling
Janeway C, Medzhitov R. Viral interference with IL-1 and Toll signaling. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 10682-10683. PMID: 11005852, PMCID: PMC34044, DOI: 10.1073/pnas.97.20.10682.Peer-Reviewed Original ResearchRecognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88
Schnare M, Holt† A, Takeda K, Akira S, Medzhitov R. Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88. Current Biology 2000, 10: 1139-1142. PMID: 10996797, DOI: 10.1016/s0960-9822(00)00700-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationB-LymphocytesCpG IslandsDendritic CellsDNADrosophila ProteinsEnzyme-Linked Immunosorbent AssayInterleukin-6Macrophages, PeritonealMembrane GlycoproteinsMiceMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicSignal TransductionToll-Like Receptor 2Toll-Like Receptor 4Toll-Like ReceptorsConceptsPathogen-associated molecular patternsPattern recognition receptorsInnate immune systemBacterial DNAFungal cell wallParticular sequence motifsParticular sequence contextCpG DNAToll-like receptorsAdaptor proteinSequence motifsAdaptor protein MyD88Signal transductionInnate immune recognitionToll familyCell wallSequence contextMolecular patternsDNAUnmethylated CpGRecognition receptorsProtein MyD88Immune systemPeptidoglycanDiverse groupHow does the immune system distinguish self from nonself?
Medzhitov R, Janeway C. How does the immune system distinguish self from nonself? Seminars In Immunology 2000, 12: 185-188. PMID: 10910738, DOI: 10.1006/smim.2000.0230.Peer-Reviewed Original ResearchLarge-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors
Gatti E, Velleca M, Biedermann B, Ma W, Unternaehrer J, Ebersold M, Medzhitov R, Pober J, Mellman I. Large-Scale Culture and Selective Maturation of Human Langerhans Cells from Granulocyte Colony-Stimulating Factor-Mobilized CD34+ Progenitors. The Journal Of Immunology 2000, 164: 3600-3607. PMID: 10725716, DOI: 10.4049/jimmunol.164.7.3600.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, CD1Antigens, CD34Antigens, Differentiation, T-LymphocyteAntigens, NeoplasmCD40 LigandCell CountCell Culture TechniquesCell DifferentiationDendritic CellsGranulocyte Colony-Stimulating FactorHematopoietic Stem Cell TransplantationHumansImmunophenotypingLangerhans CellsLeukapheresisLigandsLipopolysaccharidesMembrane GlycoproteinsStem CellsTumor Necrosis Factor-alphaConceptsDendritic cellsLangerhans cellsT cell stimulationG-CSF-mobilized patientsManipulation of DCsImmature dendritic cellsIL-12 productionPrimary immune responseHuman Langerhans cellsCell stimulationDifferent proinflammatory stimuliToll family receptorsDC preparationsMaturation stimuliTNF-alphaCD40 ligandMHC productsImmune responseBirbeck granulesProinflammatory stimuliCytokine removalFamily receptorsAg processingDC typesHomogenous population
1999
Innate immunity: Lipoproteins take their Toll on the host
Janeway C, Medzhitov R. Innate immunity: Lipoproteins take their Toll on the host. Current Biology 1999, 9: r879-r882. PMID: 10607553, DOI: 10.1016/s0960-9822(00)80073-1.Peer-Reviewed Original ResearchECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway
Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway C, Ghosh S. ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. Genes & Development 1999, 13: 2059-2071. PMID: 10465784, PMCID: PMC316957, DOI: 10.1101/gad.13.16.2059.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAnimalsBiological EvolutionCell Line, TransformedCloning, MolecularDrosophilaDrosophila ProteinsEnzyme ActivationHumansInsect ProteinsMAP Kinase Kinase Kinase 1Membrane GlycoproteinsMiceMolecular Sequence DataNF-kappa BProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesProteinsReceptors, Cell SurfaceReceptors, ImmunologicReceptors, Interleukin-1Saccharomyces cerevisiaeSignal TransductionTNF Receptor-Associated Factor 6Toll-Like ReceptorsToll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium
Frantz S, Kobzik L, Kim Y, Fukazawa R, Medzhitov R, Lee R, Kelly R. Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. Journal Of Clinical Investigation 1999, 104: 271-280. PMID: 10430608, PMCID: PMC408420, DOI: 10.1172/jci6709.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCD4 AntigensCells, CulturedCloning, MolecularCoronary VesselsDNA, ComplementaryDrosophila ProteinsGene Expression RegulationHeart FailureHeart VentriclesHumansImmunohistochemistryInterferon-gammaInterleukin-1LipopolysaccharidesMaleMembrane GlycoproteinsMiceMice, Inbred C57BLMolecular Sequence DataMyocardial InfarctionMyocardiumNF-kappa BNitric Oxide SynthaseNitric Oxide Synthase Type IIOrgan SpecificityRatsRats, Sprague-DawleyReceptors, Cell SurfaceRNA, MessengerToll-Like Receptor 4Toll-Like ReceptorsTranscription Factor AP-1ConceptsHuman Toll-like receptor 4Cardiac myocytesIL-1betaHuman myocardiumToll-like receptor 4Coronary microvascular endothelial cellsInnate immune response proteinsCytokine-inducible isoformTLR4 expression levelsNitric oxide synthaseMicrovascular endothelial cellsHearts of humansTLR4 stainingTLR4 expressionHeart failureTLR4 mRNAIschemic injuryReceptor 4Oxide synthaseImmune response proteinsControl myocardiumInnate immunityToll homologuesExperimental animalsMyocardiumThe Toll-receptor family and control of innate immunity
Kopp E, Medzhitov R. The Toll-receptor family and control of innate immunity. Current Opinion In Immunology 1999, 11: 13-18. PMID: 10047546, DOI: 10.1016/s0952-7915(99)80003-x.Peer-Reviewed Original ResearchConceptsInducible immune response genesToll receptor familyToll receptorTransduction pathwaysImmune response genesHost defense systemInnate immune recognitionMicrobial pathogensGermline-encoded receptorsNuclear factor-kappaBMolecular patternsDefense systemInnate immunityFactor-kappaBImmune recognitionPathwayReceptorsInsectsMammalsGenesPlantsPathogensExpressionKappaBFamilyInnate immune induction of the adaptive immune response.
Medzhitov R, Janeway C. Innate immune induction of the adaptive immune response. Cold Spring Harbor Symposia On Quantitative Biology 1999, 64: 429-35. PMID: 11232318, DOI: 10.1101/sqb.1999.64.429.Peer-Reviewed Original ResearchAdaptation, PhysiologicalAdaptor Proteins, Signal TransducingAdjuvants, ImmunologicAnimalsAntigens, DifferentiationDrosophila ProteinsHumansImmunityInsect ProteinsMembrane GlycoproteinsMyeloid Differentiation Factor 88NF-kappa BProtein Serine-Threonine KinasesReceptors, Cell SurfaceReceptors, ImmunologicReceptors, Interleukin-1Receptors, Tumor Necrosis FactorSignal TransductionToll-Like Receptors
1998
Innate immune recognition and control of adaptive immune responses
Medzhitov R, Janeway C. Innate immune recognition and control of adaptive immune responses. Seminars In Immunology 1998, 10: 351-353. PMID: 9799709, DOI: 10.1006/smim.1998.0136.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen-Presenting CellsCD40 LigandHumansImmune ToleranceImmunityInfectionsLymphocyte ActivationLymphocytesMembrane GlycoproteinsMyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways
Medzhitov R, Preston-Hurlburt P, Kopp E, Stadlen A, Chen C, Ghosh S, Janeway C. MyD88 Is an Adaptor Protein in the hToll/IL-1 Receptor Family Signaling Pathways. Molecular Cell 1998, 2: 253-258. PMID: 9734363, DOI: 10.1016/s1097-2765(00)80136-7.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationDrosophilaDrosophila ProteinsHumansInterleukin-1 Receptor-Associated KinasesMembrane GlycoproteinsMembrane ProteinsMyeloid Differentiation Factor 88NF-kappa BProtein KinasesProteinsReceptors, Cell SurfaceReceptors, ImmunologicReceptors, Interleukin-1Signal TransductionTNF Receptor-Associated Factor 6Toll-Like ReceptorsTranscription Factor AP-1ConceptsIL-1R familyNF-kappaB activationNF-kappaB pathwayImmune response genesToll/IL-1R familyAP-1 activationImmune responseIL-1RTRAF6 proteinInnate immunityNF-kappaBMyD88Drosophila Toll proteinReceptor familyToll receptorAdaptor proteinSignaling pathwaysReceptorsActivationToll proteinRegulator moleculesResponse genesAdult DrosophilaPathwayProtein
1997
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov R, Preston-Hurlburt P, Janeway C. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997, 388: 394-397. PMID: 9237759, DOI: 10.1038/41131.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsB7-1 AntigenCell LineCloning, MolecularDrosophilaDrosophila ProteinsHumansImmunityInsect ProteinsInterleukinsJurkat CellsMembrane GlycoproteinsMembrane ProteinsMiceMolecular Sequence DataMutationNF-kappa BReceptors, Cell SurfaceReceptors, ImmunologicRecombinant Fusion ProteinsSequence Homology, Amino AcidSignal TransductionT-LymphocytesToll-Like ReceptorsTransfectionConceptsDrosophila Toll proteinToll proteinCytoplasmic domainDrosophila TollHuman homologueLeucine-rich repeat domainNF-κB-controlled genesHuman cell linesRepeat domainActive mutantExtracellular domainNF-κBImmune responseInnate immune responseCo-stimulatory molecules B7.1Adaptive immune systemComponents of immunityInflammatory cytokines IL-1ProteinCell linesCo-stimulatory moleculesAntigen-presenting cellsAdaptive immune responsesNaive T cellsHomologues