2021
A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntiviral AgentsCOVID-19COVID-19 Drug TreatmentDisease Models, AnimalImmunity, InnateInterferon Type IMiceMice, Inbred BALB CRNASARS-CoV-2ConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacy
2009
Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function
la Sala A, He J, Laricchia-Robbio L, Gorini S, Iwasaki A, Braun M, Yap GS, Sher A, Ozato K, Kelsall B. Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function. Journal Of Experimental Medicine 2009, 206: 1227-1235. PMID: 19487420, PMCID: PMC2715075, DOI: 10.1084/jem.20080912.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8 AntigensCD8-Positive T-LymphocytesCell DifferentiationCells, CulturedCholera ToxinCyclic AMPDendritic CellsFemaleGTP-Binding Protein alpha Subunits, GsHumansInterferon Regulatory Factor-1Interferon Regulatory FactorsInterferon-gammaInterleukin-12Interleukin-12 Subunit p40MiceMice, Inbred BALB CSpleenToxoplasmosisConceptsIL-12 productionDendritic cellsPlasmacytoid DCsCholera toxinSerum IL-12 levelsIL-12 levelsPlasmacytoid dendritic cellsConventional dendritic cellsIL-12p40 promoterDendritic cell differentiationConventional DCsP40 gene expressionBone marrow cellsInterferon regulatory factor 8Regulatory factor 8Th1 responseDC differentiationIL-12p35Lymphoid organsToxoplasma gondiiMarrow cellsDibutyryl cAMPIRF8Factor 8Common mechanism
2008
Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node
Thompson JM, Nicholson MG, Whitmore AC, Zamora M, West A, Iwasaki A, Staats HF, Johnston RE. Nonmucosal Alphavirus Vaccination Stimulates a Mucosal Inductive Environment in the Peripheral Draining Lymph Node. The Journal Of Immunology 2008, 181: 574-585. PMID: 18566424, PMCID: PMC3603373, DOI: 10.4049/jimmunol.181.1.574.Peer-Reviewed Original ResearchConceptsDraining Lymph NodesVirus replicon particlesMucosal immune responsesMucosal lymphoid tissuesImmune inductionAg deliveryIgA AbsLymph nodesLymphoid tissueImmune responseMucosal surfacesMucosal addressin cell adhesion molecule-1Strong mucosal immune responsesEncephalitis virus replicon particlesCell adhesion molecule-1Multiple mucosal surfacesViral-based vaccinesAdhesion molecule-1Lymphoid structuresIL-6Immunological parametersImmunological componentsCC chemokinesIgA detectionReplicon particles
2005
Innate control of adaptive immunity via remodeling of lymph node feed arteriole
Soderberg KA, Payne GW, Sato A, Medzhitov R, Segal SS, Iwasaki A. Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 16315-16320. PMID: 16260739, PMCID: PMC1283434, DOI: 10.1073/pnas.0506190102.Peer-Reviewed Original ResearchConceptsLymph nodesNaïve lymphocytesAdaptive immunityInnate controlFeed arteriolesLocal lymph nodesSecondary lymphoid organsAntigen-specific stimulationInnate immune recognitionAntigen-specific lymphocytesPathogen-derived antigensAdaptive immune systemCognate lymphocytesLymphocyte recruitmentLymphoid organsForeign antigensImmune recognitionImmune systemCognate antigenLymphocytesVascular inputRare antigen-specific lymphocytesAntigenArteriolesImmunity
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 cellsIn Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa
Linehan MM, Richman S, Krummenacher C, Eisenberg RJ, Cohen GH, Iwasaki A. In Vivo Role of Nectin-1 in Entry of Herpes Simplex Virus Type 1 (HSV-1) and HSV-2 through the Vaginal Mucosa. Journal Of Virology 2004, 78: 2530-2536. PMID: 14963155, PMCID: PMC369262, DOI: 10.1128/jvi.78.5.2530-2536.2004.Peer-Reviewed Original ResearchConceptsHSV-2HSV-1Viral entryNectin-1Genital herpesGenital mucosaVaginal epitheliumVaginal mucosaHerpes simplex virus type 2Simplex virus type 2Primary genital herpesHerpes simplex virus type 1Mouse vaginal epitheliumFemale genital tractSimplex virus type 1Virus type 1Virus type 2Intravaginal inoculationHSV infectionMenstrual cycleVaginal infectionsGenital tractMouse modelEstrous cycleType 2
2003
CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells
Sato A, Hashiguchi M, Toda E, Iwasaki A, Hachimura S, Kaminogawa S. CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells. The Journal Of Immunology 2003, 171: 3684-3690. PMID: 14500666, DOI: 10.4049/jimmunol.171.7.3684.Peer-Reviewed Original ResearchConceptsPP dendritic cellsNaive B cellsDendritic cellsIL-6B cellsIgA secretionDC subsetsIgA productionPeyer's patch dendritic cellsSecrete IL-6Exogenous IL-6Cell coculture systemDC populationsLymphoid organsCytokine secretionAb productionT cellsHigh levelsSpleenSecretionCoculture systemCellsIgAUnique roleDistinct capacitiesCCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer’s Patch CD11b+ Dendritic Cells
Zhao X, Sato A, Dela Cruz CS, Linehan M, Luegering A, Kucharzik T, Shirakawa AK, Marquez G, Farber JM, Williams I, Iwasaki A. CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer’s Patch CD11b+ Dendritic Cells. The Journal Of Immunology 2003, 171: 2797-2803. PMID: 12960300, DOI: 10.4049/jimmunol.171.6.2797.Peer-Reviewed Original ResearchConceptsFollicle-associated epitheliumCCR6-deficient miceSubepithelial dome regionDendritic cellsPeyer's patchesMouse Peyer's patchesCCR6-/- miceDC recruitmentChemokine CCL20DC numbersAb neutralizationCCL9Villus epitheliumCCL20RT-PCRChemotaxis assaysProtein levelsMiceEpitheliumCCR6Vivo distributionImmunofluorescence analysisChemokinesSignificant reductionPutative receptorVaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2
Zhao X, Deak E, Soderberg K, Linehan M, Spezzano D, Zhu J, Knipe DM, Iwasaki A. Vaginal Submucosal Dendritic Cells, but Not Langerhans Cells, Induce Protective Th1 Responses to Herpes Simplex Virus-2. Journal Of Experimental Medicine 2003, 197: 153-162. PMID: 12538655, PMCID: PMC2193810, DOI: 10.1084/jem.20021109.Peer-Reviewed Original ResearchConceptsSubmucosal dendritic cellsDendritic cellsLymph nodesHSV-2T cellsIFNgamma secretionLangerhans cellsVaginal mucosaHerpes simplex virus type 2 infectionSimplex virus type 2 infectionViral peptidesProtective Th1 immune responseVirus type 2 infectionHerpes simplex virus 2Genital mucosal surfacesHSV-2 infectionProtective Th1 responseTh1 immune responseMHC class II moleculesProtective Th1 immunityAntigen-presenting cellsType 2 infectionSimplex virus 2Class II moleculesDC populations
2001
Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells
Iwasaki A, Kelsall B. Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells. The Journal Of Immunology 2001, 166: 4884-4890. PMID: 11290765, DOI: 10.4049/jimmunol.166.8.4884.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDB7-1 AntigenB7-2 AntigenCD8 AntigensCell LineageCell SeparationDendritic CellsEpithelial CellsEpitopes, T-LymphocyteFemaleHistocompatibility Antigens Class IIImmunophenotypingInterferon-gammaInterleukin-10Interleukin-12Interleukin-4Lectins, C-TypeLymphocyte ActivationLymphocyte SubsetsMacrophage-1 AntigenMembrane GlycoproteinsMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicMinor Histocompatibility AntigensMyeloid CellsPeyer's PatchesReceptors, Cell SurfaceSpleenT-LymphocytesUp-RegulationConceptsMyeloid dendritic cellsDendritic cellsCD40 ligand trimerDC subsetsIL-12p70IL-10T cellsPeyer's patch dendritic cellsIFN-gamma productionSoluble CD40 ligand trimerMucosal lymphoid tissuesNaive T cellsFollicle-associated epitheliumMurine Peyer's patchesNonmucosal sitesDC subpopulationsSubepithelial domeIL-4Lymphoid tissuePeyer's patchesMicrobial stimuliInterfollicular regionsIFN-gammaSurface phenotypeMucosal tissues
2000
Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells
Gurunathan S, Stobie L, Prussin C, Sacks D, Glaichenhaus N, Iwasaki A, Fowell D, Locksley R, Chang J, Wu C, Seder R. Requirements for the Maintenance of Th1 Immunity In Vivo Following DNA Vaccination: A Potential Immunoregulatory Role for CD8+ T Cells. The Journal Of Immunology 2000, 165: 915-924. PMID: 10878366, DOI: 10.4049/jimmunol.165.2.915.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, ProtozoanCD4 Lymphocyte CountCD4-Positive T-LymphocytesCD8 AntigensCD8-Positive T-LymphocytesCell DivisionCells, CulturedDNA, ProtozoanGenes, T-Cell Receptor betaImmune SeraImmunity, CellularInjections, SubcutaneousInterferon-gammaInterleukin-12Leishmania majorLeishmaniasis, CutaneousLymph NodesLymphocyte ActivationMiceMice, Inbred BALB CMice, TransgenicProtein Kinase CProtozoan ProteinsReceptors, InterleukinReceptors, Interleukin-12Th1 CellsVaccines, DNAConceptsIFN-gamma-producing T cellsDepletion of CD8DNA-vaccinated miceT cellsDNA vaccinationProtective immunityImmunoregulatory roleWk postvaccinationLong-term protective immunityLACK-specific CD4Time of vaccinationPotential immunoregulatory roleNovel immunoregulatory roleTh1 immunityIL-12Th1 cellsInfectious challengeCD8VaccinationInfectionLeishmania majorStriking decreaseMiceImmunityPostvaccinationPrimary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses
He J, Gurunathan S, Iwasaki A, Ash-Shaheed B, Kelsall B. Primary Role for GI Protein Signaling in the Regulation of Interleukin 12 Production and the Induction of T Helper Cell Type 1 Responses. Journal Of Experimental Medicine 2000, 191: 1605-1610. PMID: 10790434, PMCID: PMC2213427, DOI: 10.1084/jem.191.9.1605.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Diphosphate RiboseAnimalsCD8 AntigensCell DifferentiationDendritic CellsGTP-Binding Protein alpha Subunits, Gi-GoInterferon-gammaInterleukin-10Interleukin-12Interleukin-4Leishmaniasis, CutaneousLymph NodesMiceMice, Inbred BALB CMice, Mutant StrainsPertussis ToxinProtein Processing, Post-TranslationalSignal TransductionSpleenTh1 CellsTumor Necrosis Factor-alphaVirulence Factors, BordetellaConceptsPertussis toxinGi-protein signalingTh1 responseIL-12T helper cell type 1 responseGi proteinsNormal BALB/c miceBALB/c miceLymphoid dendritic cellsIL-12 productionInterleukin-12 productionType 1 responseCapacity of splenocytesIL-12 p40Tumor necrosis factorRegulation of interleukinT cell differentiationNonmicrobial stimuliDendritic cellsIL-10Lymph nodesC miceTNF-alphaNecrosis factorProtein signalingLocalization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine
Iwasaki A, Kelsall B. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine. Journal Of Experimental Medicine 2000, 191: 1381-1394. PMID: 10770804, PMCID: PMC2193144, DOI: 10.1084/jem.191.8.1381.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceChemokine CCL19Chemokine CCL20Chemokines, CCChemotaxisDendritic CellsDNA PrimersFemaleGene ExpressionIn Situ HybridizationMacrophage Inflammatory ProteinsMiceMice, Inbred BALB CMicroscopy, ConfocalModels, BiologicalPeyer's PatchesReceptors, CCR6Receptors, CCR7Receptors, ChemokineRNA, MessengerSpleenConceptsDendritic cell subsetsInterfollicular regionsDC subsetsCell subsetsInflammatory proteinPeyer's patchesSecondary lymphoid organ chemokineChemokine macrophage inflammatory proteinSplenic DC subsetsSubepithelial dome regionDistinct dendritic cell subsetsRole of chemokinesT cell responsesMacrophage inflammatory proteinT-cell regionsFollicle-associated epitheliumMurine Peyer's patchesTranscriptase-polymerase chain reaction analysisFunctional CCR7Lymphoid DCsMIP-3βPP DCsMyeloid DCsCCR7 expressionPolymerase chain reaction analysis
1999
Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells
Iwasaki A, Kelsall B. Freshly Isolated Peyer's Patch, but Not Spleen, Dendritic Cells Produce Interleukin 10 and Induce the Differentiation of T Helper Type 2 Cells. Journal Of Experimental Medicine 1999, 190: 229-240. PMID: 10432286, PMCID: PMC2195574, DOI: 10.1084/jem.190.2.229.Peer-Reviewed Original ResearchConceptsPP dendritic cellsDendritic cellsNaive T cellsPeyer's patchesT cellsIL-10DC populationsImmune responseT cell receptor transgenic miceAllogeneic T cell proliferationT helper type 2 cellsT helper cell responsesMajor histocompatibility complex (MHC) class II moleculesIsolated Peyer's patchesSurface phenotypic analysisVivo dendritic cellsHelper cell responsesIL-10 secretionPrime T cellsDistinct immune responsesReceptor transgenic miceAntigen-presenting cellsIFN-gamma productionProduction of interleukinT cell proliferation