2022
Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease
Jayewickreme R, Mao T, Philbrick W, Kong Y, Treger RS, Lu P, Rakib T, Dong H, Dang-Lawson M, Guild WA, Lau TJ, Iwasaki A, Tokuyama M. Endogenous Retroviruses Provide Protection Against Vaginal HSV-2 Disease. Frontiers In Immunology 2022, 12: 758721. PMID: 35058919, PMCID: PMC8764156, DOI: 10.3389/fimmu.2021.758721.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEndogenous RetrovirusesFemaleHerpes GenitalisHerpesvirus 2, HumanMiceMice, KnockoutVaginal DiseasesConceptsHSV-2 infectionHSV-2 diseaseHerpes simplex virus type 2 infectionSimplex virus type 2 infectionEnhanced type I interferonIntravaginal HSV-2 infectionVaginal HSV-2 infectionVirus type 2 infectionEndogenous retrovirusesReceptor-deficient miceType 2 infectionHigh systemic levelsWildtype C57BL/6 miceType I interferonTLR7-/- miceC57BL/6 miceInfectious endogenous retrovirusDeficient miceIntravaginal applicationAntiviral immunityI interferonVaginal tissueDetrimental functionsTLR7Mice
2021
B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection
Gehlhausen JR, Iwasaki A. B cells join T cell clusters in the host response to recurrent herpes simplex virus 2 infection. Journal Of Clinical Investigation 2021, 131: e148300. PMID: 33938452, PMCID: PMC8087191, DOI: 10.1172/jci148300.Peer-Reviewed Original ResearchConceptsAntibody-secreting cellsB cellsRecurrent lesionsHerpes simplex virus 2 infectionHSV-2-specific antibodiesRecurrent genital herpes lesionsSimplex virus 2 infectionGenital herpes lesionsHSV-2 lesionsVirus 2 infectionT cell clustersSkin biopsy specimensB cell subsetsB cell populationsNaive B cellsStage of infectionLesion reactivationDisease resolutionImmune infiltratesAntibody levelsHerpes lesionsCell subsetsBiopsy specimensHost responseLesions
2019
Migrant memory B cells secrete luminal antibody in the vagina
Oh JE, Iijima N, Song E, Lu P, Klein J, Jiang R, Kleinstein SH, Iwasaki A. Migrant memory B cells secrete luminal antibody in the vagina. Nature 2019, 571: 122-126. PMID: 31189952, PMCID: PMC6609483, DOI: 10.1038/s41586-019-1285-1.Peer-Reviewed Original ResearchConceptsMemory B cellsFemale reproductive tractB cellsPlasma cellsReproductive tractCD4 tissue-resident memory T cellsTissue-resident memory T cellsLower female reproductive tractHerpes simplex virus 2Genital herpes infectionMemory T cellsExpression of chemokinesSimplex virus 2CXCR3-dependent mannerLocal plasma cellsLuminal antibodyMucosal antibodiesHerpes infectionPrimary infectionMucosal barrierSecondary challengeVariety of pathogensT cellsLamina propriaInducible source
2016
CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2
Shin H, Kumamoto Y, Gopinath S, Iwasaki A. CD301b+ dendritic cells stimulate tissue-resident memory CD8+ T cells to protect against genital HSV-2. Nature Communications 2016, 7: 13346. PMID: 27827367, PMCID: PMC5105190, DOI: 10.1038/ncomms13346.Peer-Reviewed Original ResearchConceptsCD8 TRM cellsAntigen-presenting cellsGenital HSV-2 infectionTissue-resident memory CD8HSV-2 infectionTRM cellsDendritic cellsMemory CD8Protective immunityT cellsPopulations of APCsGenital HSV-2Protective immune responseFemale genital tractMHC class IHSV-2Genital tractAntigen presentationImmune responseLamina propriaViral infectionConfer protectionBarrier tissuesClass IInfectionAccess of protective antiviral antibody to neuronal tissues requires CD4 T-cell help
Iijima N, Iwasaki A. Access of protective antiviral antibody to neuronal tissues requires CD4 T-cell help. Nature 2016, 533: 552-556. PMID: 27225131, PMCID: PMC4883597, DOI: 10.1038/nature17979.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralB-LymphocytesBiological TransportBlood-Brain BarrierCapillary PermeabilityCD4-Positive T-LymphocytesDisease Models, AnimalFemaleGanglia, SpinalHerpes GenitalisHerpesvirus 2, HumanHistocompatibility Antigens Class IImmunologic MemoryIntegrin alpha4Interferon-gammaMiceNerve TissueNervous SystemNeuronsNoseReceptors, FcSpinal CordVesiculovirus
2014
A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells
Iijima N, Iwasaki A. A local macrophage chemokine network sustains protective tissue-resident memory CD4 T cells. Science 2014, 346: 93-98. PMID: 25170048, PMCID: PMC4254703, DOI: 10.1126/science.1257530.Peer-Reviewed Original ResearchConceptsMemory lymphocyte clustersMemory T cellsT cellsCD8 tissue-resident memory T cellsTissue-resident memory CD4 T cellsHerpes simplex virus 2 infectionTissue-resident memory T cellsSimplex virus 2 infectionMemory CD4 T cellsEfficient local controlPool of CD4Role of CD4CD4 T cellsVirus 2 infectionVaginal CD4Parabiotic miceGenital mucosaVaccine strategiesChemokine networkLymphocyte clustersHSV-2Viral infectionCD4Local controlInfection
2010
Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue
Iijima N, Mattei LM, Iwasaki A. Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 108: 284-289. PMID: 21173243, PMCID: PMC3017177, DOI: 10.1073/pnas.1005201108.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntigen-Presenting CellsCell DifferentiationCytokinesEnzyme-Linked Immunospot AssayFemaleFluorescein-5-isothiocyanateHerpes GenitalisHerpesvirus 2, HumanInterferon-gammaMiceMice, Inbred C57BLMice, KnockoutMonocytesReceptor, Interferon alpha-betaReceptors, CCR2Th1 CellsConceptsMonocyte-derived APCTh1 immunityInflammatory monocytesTh1 cellsCD4 T cell primingHerpes simplex virus 2Effector Th1 cellsMemory Th1 cellsPrimary mucosal infectionSecondary viral challengeT cell primingIFN-γ secretionSimplex virus 2Signs of infectionImportance of monocytesAPC subsetsCell primingDendritic cellsMucosal infectionsViral challengePeripheral tissuesMucosal tissuesAntiviral protectionMonocytesInfectionIn Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells
Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, Mizushima N, Grinstein S, Iwasaki A. In Vivo Requirement for Atg5 in Antigen Presentation by Dendritic Cells. Immunity 2010, 32: 227-239. PMID: 20171125, PMCID: PMC2996467, DOI: 10.1016/j.immuni.2009.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationAutophagy-Related Protein 5Cells, CulturedDendritic CellsFemaleHerpes SimplexHerpesvirus 2, HumanHistocompatibility Antigens Class IILymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsRadiation ChimeraRNA, Small InterferingConceptsMHC-II presentationMHC class IIDendritic cellsAntigen presentationClass IIHerpes simplex virus infectionToll-like receptor stimuliT cell primingSimplex virus infectionCell primingAbsence of ATG5Microbial antigensVirus infectionMHC ICytosolic antigensConditional deletionAntigenReceptor stimuliAutophagic machineryKey autophagy genesRapid diseasePresentationATG5Lysosome fusionAutophagy genes
2009
CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help
Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature 2009, 462: 510-513. PMID: 19898495, PMCID: PMC2789415, DOI: 10.1038/nature08511.Peer-Reviewed Original ResearchConceptsT cell helpT cellsRecruitment of CD8Activity of CD4T lymphocyte responsesT helper cellsSecretion of interferonLymphocyte mobilizationCD4 helpCTL responsesCytotoxic CD8Lymphocyte responsesMucosal sitesChemokine secretionHelper cellsVirus-infected tissuesViral infectionCD4CD8Intracellular pathogensSecretionUnrecognized aspectsCellsInterferonInfection
2008
Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus
Iijima N, Linehan MM, Zamora M, Butkus D, Dunn R, Kehry MR, Laufer TM, Iwasaki A. Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. Journal Of Experimental Medicine 2008, 205: 3041-3052. PMID: 19047439, PMCID: PMC2605233, DOI: 10.1084/jem.20082039.Peer-Reviewed Original ResearchConceptsMemory Th1 cellsDendritic cellsTh1 cellsB cellsIFN-gammaHerpes simplex virus 2 infectionAntiviral protectionSimplex virus 2 infectionMemory CD4 T cellsFurther viral replicationTh1 memory responseHSV-2 infectionCD4 T cellsLocal dendritic cellsVirus 2 infectionAntigen-presenting cellsCytotoxic T lymphocytesMHC class IISite of infectionHerpes simplex virusTh1 responseImmunized miceRecall responsesViral antigensMHC class
2006
Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ
Lund JM, Linehan MM, Iijima N, Iwasaki A. Cutting Edge: Plasmacytoid Dendritic Cells Provide Innate Immune Protection against Mucosal Viral Infection In Situ. The Journal Of Immunology 2006, 177: 7510-7514. PMID: 17114418, DOI: 10.4049/jimmunol.177.11.7510.Peer-Reviewed Original ResearchConceptsMucosal viral infectionsPlasmacytoid dendritic cellsPlasmacytoid DCsDendritic cellsViral infectionGenital HSV-2 infectionHSV-2 infectionLocal viral replicationAntiviral effector cellsInnate immune protectionTLR9-dependent mannerType I IFNsType I IFNPeripheral mucosaPowerful APCsTh1 immunityEffector cellsImmune protectionNaive lymphocytesAdaptive immunityI IFNsI IFNVaginal mucosaViral replicationInnate defense
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 cellsMAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection
Soderberg KA, Linehan MM, Ruddle NH, Iwasaki A. MAdCAM-1 Expressing Sacral Lymph Node in the Lymphotoxin β-Deficient Mouse Provides a Site for Immune Generation Following Vaginal Herpes Simplex Virus-2 Infection. The Journal Of Immunology 2004, 173: 1908-1913. PMID: 15265924, DOI: 10.4049/jimmunol.173.3.1908.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralCD4-Positive T-LymphocytesCell Adhesion MoleculesDendritic CellsFemaleHerpes GenitalisHerpesvirus 2, HumanImmunoglobulin GImmunoglobulinsLymph NodesLymphocyte ActivationLymphotoxin-alphaLymphotoxin-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMucoproteinsSacrococcygeal RegionSplenectomyT-Cell Antigen Receptor SpecificityTh1 CellsVaginitisConceptsBeta-deficient miceSacral lymph nodesLymph nodesMesenteric lymph nodesWild-type miceGenital mucosaHerpes simplex virus 2 infectionIntravaginal HSV-2 infectionLT alpha-deficient miceMucosal addressin cell adhesion molecule-1Simplex virus 2 infectionCell adhesion molecule-1Mucosal lymph nodesAlpha-deficient miceCervical lymph nodesHSV-2 infectionVirus 2 infectionHSV type 2Potent immune responsesAdhesion molecule-1Intravaginal infectionTh1 responseDendritic cellsIgG responsesIliac arteryIn 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
The role of dendritic cells in immune responses against vaginal infection by herpes simplex virus type 2
Iwasaki A. The role of dendritic cells in immune responses against vaginal infection by herpes simplex virus type 2. Microbes And Infection 2003, 5: 1221-1230. PMID: 14623018, DOI: 10.1016/j.micinf.2003.09.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDendritic CellsFemaleHerpes LabialisHerpes SimplexHerpesvirus 2, HumanHumansImmunityVaginal DiseasesConceptsHerpes simplex virus type 2Simplex virus type 2Virus type 2Dendritic cellsType 2Female genital mucosaSpecialized dendritic cellsEffector immunityGenital ulcersGenital herpesGenital infectionGenital mucosaProtective immunityLeading causeVaginal infectionsImmune responseAdaptive immunityMore womenImmunityRecent evidenceInfectionSpecific subsetCellsUlcersHerpesToll-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 A1Vaginal 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