2001
Recognition 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 protein
2000
Innate immune recognition: mechanisms and pathways
Medzhitov R, Janeway C. Innate immune recognition: mechanisms and pathways. Immunological Reviews 2000, 173: 89-97. PMID: 10719670, DOI: 10.1034/j.1600-065x.2000.917309.x.Peer-Reviewed Original ResearchConceptsPattern recognition receptorsInnate immune systemMost multicellular organismsRecognition receptorsMulticellular organismsHost defenseInducible responsesImmune response genesResponse genesPathogen recognitionImmune systemMolecular patternsInfectious microbesAncient formPathwayReceptorsDefenseGenesMicrobesOrganismsMicroorganismsLarge groupPathogensExpressionPatterns
1999
ECSIT 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
MyD88 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