2014
A Promiscuous Lipid-Binding Protein Diversifies the Subcellular Sites of Toll-like Receptor Signal Transduction
Bonham KS, Orzalli MH, Hayashi K, Wolf AI, Glanemann C, Weninger W, Iwasaki A, Knipe DM, Kagan JC. A Promiscuous Lipid-Binding Protein Diversifies the Subcellular Sites of Toll-like Receptor Signal Transduction. Cell 2014, 156: 705-716. PMID: 24529375, PMCID: PMC3951743, DOI: 10.1016/j.cell.2014.01.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MembraneEndosomesHerpes SimplexImmunity, InnateMacrophagesMembrane GlycoproteinsMice, Inbred C57BLMyeloid Differentiation Factor 88Receptors, Interleukin-1Signal TransductionToll-Like ReceptorsConceptsToll-like receptorsToll-like receptor signal transductionSignal transductionDifferent organellesProinflammatory cytokine expressionSubcellular sitesInnate immune signal transductionInnate immune systemPhosphoinositide-binding domainsImmune signal transductionLipid binding proteinMultiple subcellular locationsReceptor signal transductionCytokine expressionLipid targetsImmune systemInnate immunityHost defenseProtein complexesSubcellular locationPlasma membraneAdaptor TIRAPTIRAPNatural activatorFamily members
2013
IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus
Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus. Nature Immunology 2013, 14: 246-253. PMID: 23314004, PMCID: PMC3577947, DOI: 10.1038/ni.2514.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell MovementDendritic CellsInfluenza A virusInterleukin-1Lymphocyte ActivationMembrane GlycoproteinsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Nerve Tissue ProteinsOrthomyxoviridae InfectionsReceptors, CCR7Receptors, Cell SurfaceReceptors, Interleukin-1Receptors, Pattern RecognitionSignal TransductionToll-Like Receptor 7
2012
MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, Medzhitov R. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nature Communications 2012, 3: 1120. PMID: 23047678, PMCID: PMC3521499, DOI: 10.1038/ncomms2113.Peer-Reviewed Original ResearchConceptsToll-like receptorsInterleukin-10Mononuclear phagocytesIL-10-deficient miceT helper 17 responsesColonic mononuclear phagocytesDevelopment of colitisInflammatory bowel diseaseColitis developmentBowel diseaseInterleukin-23MyD88 expressionInterleukin-1βInterleukin-6Intestinal homeostasisEpithelial expressionMyD88Multiple cell typesMiceCell typesReceptorsPhagocytesBacterial sensingDistinct populationsHigh levelsAdaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells
Mantegazza AR, Guttentag SH, El-Benna J, Sasai M, Iwasaki A, Shen H, Laufer TM, Marks MS. Adaptor Protein-3 in Dendritic Cells Facilitates Phagosomal Toll-like Receptor Signaling and Antigen Presentation to CD4+ T Cells. Immunity 2012, 36: 782-794. PMID: 22560444, PMCID: PMC3361531, DOI: 10.1016/j.immuni.2012.02.018.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3AnimalsAntigen PresentationAntigensCD4-Positive T-LymphocytesCell DifferentiationCell MembraneCells, CulturedDendritic CellsEndocytosisHistocompatibility Antigens Class IILigandsListeria monocytogenesListeriosisMiceMice, Inbred C57BLMice, TransgenicMyeloid Differentiation Factor 88OvalbuminPeptidesPhagocytosisPhagosomesSignal TransductionTh1 CellsToll-Like ReceptorsConceptsToll-like receptor signalingDendritic cellsAntigen presentationAdaptor protein 3Protein 3Receptor signalingMHC-II presentationEffector cell functionListeria monocytogenes infectionTLR ligandsMonocytogenes infectionTLR4 recruitmentT cellsCell activationIntracellular storesPhagolysosome maturationCell functionPearl miceReceptor-mediated endocytosisAntigenPresentationMolecular mechanismsPhagosomesCell surfaceSignaling
2010
Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3
Sasai M, Linehan MM, Iwasaki A. Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3. Science 2010, 329: 1530-1534. PMID: 20847273, PMCID: PMC3063333, DOI: 10.1126/science.1187029.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAnimalsCells, CulturedCytokinesCytoplasmic VesiclesDendritic CellsEndosomesInterferon Regulatory Factor-7Interferon Type ILysosomal-Associated Membrane Protein 2MacrophagesMembrane Transport ProteinsMiceMice, Inbred C57BLMyeloid Differentiation Factor 88OligodeoxyribonucleotidesProtein TransportRecombinant Fusion ProteinsSignal TransductionTNF Receptor-Associated Factor 3Toll-Like Receptor 9Transcriptional ActivationVesicle-Associated Membrane Protein 3ConceptsI interferonTLR9 signalsEndosomal Toll-like receptors 7Toll-like receptor 9 signalingToll-like receptor 7Protein 3Type I IFNsDependent proinflammatory cytokinesInterferon regulatory factor 7I IFNsProinflammatory cytokine genesType I interferonNuclear factor κBRegulatory factor 7Viral nucleic acidsProinflammatory cytokinesReceptor 7Factor κBCytokine genesTLR9Adaptor protein 3Intracellular mechanismsFactor 7Viral pathogensReceptor trafficking
2004
Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments
Sato A, Iwasaki A. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 16274-16279. PMID: 15534227, PMCID: PMC528964, DOI: 10.1073/pnas.0406268101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationCaspase 1Cell DifferentiationCell MovementDendritic CellsFemaleHerpesvirus 2, HumanImmunity, InnateInterleukin-12Membrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicReceptors, InterferonSignal TransductionStromal CellsTh1 CellsToll-Like ReceptorsConceptsToll-like receptorsT cell responsesPattern recognition receptorsViral infectionContribution of TLRsRecognition receptorsCell responsesEffector T cell responsesHerpes simplex virus type 2Simplex virus type 2Antiviral adaptive immunityDendritic cell compartmentEffector T cellsDendritic cell maturationMost viral infectionsVirus type 2Infected epithelial cellsMucosal infectionsT cellsAdaptive immunityAntiviral immunityInfectious agentsType 2Immune recognitionStromal cellsRecognition of single-stranded RNA viruses by Toll-like receptor 7
Lund JM, Alexopoulou L, Sato A, Karow M, Adams NC, Gale NW, Iwasaki A, Flavell RA. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 5598-5603. PMID: 15034168, PMCID: PMC397437, DOI: 10.1073/pnas.0400937101.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationBone Marrow CellsChick EmbryoChloroquineCytokinesDendritic CellsEndosomesInterferon-alphaMacrophagesMembrane GlycoproteinsMiceMice, KnockoutMyeloid Differentiation Factor 88OrthomyxoviridaePeritoneumReceptors, Cell SurfaceReceptors, ImmunologicRhabdoviridae InfectionsRNA, ViralSpleenToll-Like Receptor 7Vesicular stomatitis Indiana virusConceptsVesicular stomatitis virusRNA virusesHigh CpG contentGenomes of virusesToll-like receptorsStomatitis virusMammalian genomesGenomic nucleic acidsAdaptor protein MyD88Endocytic pathwayLigand recognitionCpG contentViral infectionTLR adaptor protein MyD88Innate immune responseToll-like receptor 7Molecular signaturesPlasmacytoid dendritic cellsInnate immune cellsProduction of cytokinesGenomeProtein MyD88Types of pathogensNucleic acidsVivo infection
2003
Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells
Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells. Journal Of Experimental Medicine 2003, 198: 513-520. PMID: 12900525, PMCID: PMC2194085, DOI: 10.1084/jem.20030162.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsAntigens, DifferentiationBone Marrow CellsCpG IslandsDendritic CellsDNA-Binding ProteinsEndosomesFemaleHerpesvirus 2, HumanHumansInterferon-alphaMaleMiceMice, Inbred StrainsMice, KnockoutMyeloid Differentiation Factor 88Receptors, Cell SurfaceReceptors, ImmunologicSignal TransductionToll-Like Receptor 9ConceptsHerpes simplex virus 2Plasmacytoid dendritic cellsIFN-alpha secretionToll-like receptorsSimplex virus 2Dendritic cellsIFN-alphaI interferonToll-like receptor 9Virus 2Adaptor molecule MyD88Type I interferonHSV-2 DNADose-dependent mannerMouse bone marrowMolecule MyD88Receptor 9Knockout miceBone marrowTLR9Potent secretorsSecretionOligonucleotide treatmentVirus recognitionBafilomycin A1