2024
Exploring new perspectives in immunology
Medzhitov R, Iwasaki A. Exploring new perspectives in immunology. Cell 2024, 187: 2079-2094. PMID: 38670066, DOI: 10.1016/j.cell.2024.03.038.Peer-Reviewed Original Research
2023
On developmental programming of the immune system
Hong J, Medzhitov R. On developmental programming of the immune system. Trends In Immunology 2023, 44: 877-889. PMID: 37852863, DOI: 10.1016/j.it.2023.09.004.Peer-Reviewed Original ResearchDistinguishing features of long COVID identified through immune profiling
Klein J, Wood J, Jaycox J, Dhodapkar R, Lu P, Gehlhausen J, Tabachnikova A, Greene K, Tabacof L, Malik A, Silva Monteiro V, Silva J, Kamath K, Zhang M, Dhal A, Ott I, Valle G, Peña-Hernández M, Mao T, Bhattacharjee B, Takahashi T, Lucas C, Song E, McCarthy D, Breyman E, Tosto-Mancuso J, Dai Y, Perotti E, Akduman K, Tzeng T, Xu L, Geraghty A, Monje M, Yildirim I, Shon J, Medzhitov R, Lutchmansingh D, Possick J, Kaminski N, Omer S, Krumholz H, Guan L, Dela Cruz C, van Dijk D, Ring A, Putrino D, Iwasaki A. Distinguishing features of long COVID identified through immune profiling. Nature 2023, 623: 139-148. PMID: 37748514, PMCID: PMC10620090, DOI: 10.1038/s41586-023-06651-y.Peer-Reviewed Original ResearchConceptsLong COVIDSARS-CoV-2Infection syndromeExaggerated humoral responseSoluble immune mediatorsEpstein-Barr virusPost-exertional malaiseCross-sectional studyHigher antibody responseImmune mediatorsImmune phenotypingImmune profilingHumoral responseAntibody responseLymphocyte populationsCOVID statusUnbiased machineCortisol levelsLC statusRelevant biomarkersViral pathogensSyndromeCOVIDFuture studiesBiological featuresModes of type 2 immune response initiation
Kopp E, Agaronyan K, Licona-Limón I, Nish S, Medzhitov R. Modes of type 2 immune response initiation. Immunity 2023, 56: 687-694. PMID: 37044059, DOI: 10.1016/j.immuni.2023.03.015.Peer-Reviewed Original ResearchAn autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis
Wang S, Li K, Pickholz E, Dobie R, Matchett K, Henderson N, Carrico C, Driver I, Borch Jensen M, Chen L, Petitjean M, Bhattacharya D, Fiel M, Liu X, Kisseleva T, Alon U, Adler M, Medzhitov R, Friedman S. An autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis. Science Translational Medicine 2023, 15: eadd3949. PMID: 36599008, PMCID: PMC10686705, DOI: 10.1126/scitranslmed.add3949.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsAdvanced hepatic fibrosisNonalcoholic steatohepatitisAdvanced fibrosisHepatic fibrosisHSC activationStellate cellsMurine nonalcoholic steatohepatitisStage-specific therapyHuman nonalcoholic steatohepatitisHuman HSC activationNeurotrophic receptor tyrosine kinaseDrug targetsSingle-nucleus RNA sequencingAdvanced diseaseAntifibrotic efficacyAntifibrotic therapyFibrosisTherapeutic paradigmAutocrine interactionsPharmacological inhibitionReceptor tyrosine kinasesSteatohepatitisStrongest predictorTherapy
2020
Longitudinal analyses reveal immunological misfiring in severe COVID-19
Lucas C, Wong P, Klein J, Castro TBR, Silva J, Sundaram M, Ellingson MK, Mao T, Oh JE, Israelow B, Takahashi T, Tokuyama M, Lu P, Venkataraman A, Park A, Mohanty S, Wang H, Wyllie AL, Vogels CBF, Earnest R, Lapidus S, Ott IM, Moore AJ, Muenker MC, Fournier JB, Campbell M, Odio CD, Casanovas-Massana A, Herbst R, Shaw A, Medzhitov R, Schulz W, Grubaugh N, Dela Cruz C, Farhadian S, Ko A, Omer S, Iwasaki A. Longitudinal analyses reveal immunological misfiring in severe COVID-19. Nature 2020, 584: 463-469. PMID: 32717743, PMCID: PMC7477538, DOI: 10.1038/s41586-020-2588-y.Peer-Reviewed Original ResearchConceptsSevere COVID-19Moderate COVID-19Immune signaturesDisease outcomeCOVID-19Disease trajectoriesInterleukin-5Early immune signaturesInnate cell lineagesType 2 effectorsT cell numbersPoor clinical outcomeWorse disease outcomesImmune response profileCoronavirus disease 2019Distinct disease trajectoriesCytokine levelsImmunological correlatesImmune profileClinical outcomesEarly elevationImmune profilingIL-13Immunoglobulin EDisease 2019
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 ResearchRecognition 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 ResearchHow 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 populationFly immunity: great expectations
Medzhitov R, Janeway C. Fly immunity: great expectations. Genome Biology 2000, 1: reviews106.1. PMID: 11104525, PMCID: PMC138838, DOI: 10.1186/gb-2000-1-1-reviews106.Peer-Reviewed Original Research
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 recognitionPathwayReceptorsInsectsMammalsGenesPlantsPathogensExpressionKappaBFamily