2020
Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy.
Gopinath S, Lu P, Iwasaki A. Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in "Prime and Pull" Vaccine Strategy. The Journal Of Immunology 2020, 204: 1703-1707. PMID: 32122994, DOI: 10.4049/jimmunol.1900462.Peer-Reviewed Original ResearchConceptsTissue-resident memory T cellsGenital herpes infectionMemory T cellsT cellsHerpes infectionVirus-specific effector T cellsVaginal applicationTopical vaginal applicationCD8 T cellsEffector T cellsProtective immune responseSingle topical applicationTopical aminoglycosidesGenital mucosaChemokine expressionVaccine strategiesImmune responseVaginal mucosaTopical applicationBarrier tissuesMiceRobust activationAminoglycoside antibioticsMucosaInfection
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
2017
TAM Receptors Are Not Required for Zika Virus Infection in Mice
Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R, Gaitsch HF, Parnell LA, Cao B, Mysorekar IU, Rothlin CV, Fikrig E, Diamond MS, Iwasaki A. TAM Receptors Are Not Required for Zika Virus Infection in Mice. Cell Reports 2017, 19: 558-568. PMID: 28423319, PMCID: PMC5485843, DOI: 10.1016/j.celrep.2017.03.058.Peer-Reviewed Original ResearchConceptsTAM receptorsZika virusAbsence of IFNARGlobal public health concernNon-pregnant miceZika virus infectionAdult female micePublic health concernZIKV entryZIKV infectionFemale miceViral inoculationZIKV replicationMertk (TAM) receptorsYoung miceVirus infectionEntry receptorViral titersViral replicationCell tropismInfectionHealth concernMiceAxlReceptors
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 IInfectionVaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL, Iwasaki A. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell 2016, 166: 1247-1256.e4. PMID: 27565347, PMCID: PMC5006689, DOI: 10.1016/j.cell.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, HabitualAnimalsBrainBrain DiseasesDisease Models, AnimalFemaleFetal Growth RetardationInterferon Regulatory Factor-3MiceMice, Inbred C57BLMice, Mutant StrainsPregnancyPregnancy Complications, InfectiousReceptor, Interferon alpha-betaVaginaVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusFetal brain infectionFetal growth restrictionLocal viral replicationWild-type miceType I interferon receptorZIKV challengeTranscription factor IRF3Vaginal exposureGenital mucosaBrain infectionWT miceEarly pregnancyZIKV infectionGrowth restrictionPregnant damsVaginal infectionsZIKV replicationFetal brainMouse modelIFN pathwayVaginal tractUnborn fetusViral replicationDisease consequencesViral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality
Khoury-Hanold W, Yordy B, Kong P, Kong Y, Ge W, Szigeti-Buck K, Ralevski A, Horvath TL, Iwasaki A. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. Cell Host & Microbe 2016, 19: 788-799. PMID: 27281569, PMCID: PMC4902295, DOI: 10.1016/j.chom.2016.05.008.Peer-Reviewed Original ResearchConceptsGenital HSV-1 infectionEnteric nervous systemHSV-1 infectionSensory nervous systemNervous systemGenital herpesToxic megacolonHSV-1Genital mucosal epithelial cellsPeripheral sensory nervous systemDorsal root gangliaPathological inflammatory responsesMucosal epithelial cellsHerpes simplex virus 1Simplex virus 1Urinary retentionEnteric neuronsLaxative treatmentAutonomic gangliaRoot gangliaInflammatory responseViral gene transcriptionMouse modelInfectionEpithelial cells
2015
Cervicovaginal Microbiota: Simple Is Better
Gopinath S, Iwasaki A. Cervicovaginal Microbiota: Simple Is Better. Immunity 2015, 42: 790-791. PMID: 25992855, DOI: 10.1016/j.immuni.2015.05.006.Peer-Reviewed Original Research
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
2012
A vaccine strategy that protects against genital herpes by establishing local memory T cells
Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491: 463-467. PMID: 23075848, PMCID: PMC3499630, DOI: 10.1038/nature11522.Peer-Reviewed Original ResearchUnique features of antiviral immune system of the vaginal mucosa
Kumamoto Y, Iwasaki A. Unique features of antiviral immune system of the vaginal mucosa. Current Opinion In Immunology 2012, 24: 411-416. PMID: 22673876, PMCID: PMC3423557, DOI: 10.1016/j.coi.2012.05.006.Peer-Reviewed Original ResearchConceptsVaginal mucosaVirus-specific CD4Development of vaccinesAntiviral immune systemHuman papillomavirusGenital tractT cellsImmune responseAdaptive immunityHuman vaccinesMucosal organsImmune systemVaccineAntiviral defenseMucosaVaginaVirusRecent studiesWide spectrumVast majorityCurrent understandingCD8CD4PapillomavirusImmunobiology
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 aspectsCellsInterferonInfectionDifferential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection
Lee HK, Zamora M, Linehan MM, Iijima N, Gonzalez D, Haberman A, Iwasaki A. Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection. Journal Of Experimental Medicine 2009, 206: 359-370. PMID: 19153243, PMCID: PMC2646574, DOI: 10.1084/jem.20080601.Peer-Reviewed Original ResearchConceptsResident dendritic cellsCD8 T cellsDendritic cellsHSV-1 infectionT cellsEpicutaneous infectionAntigen presentationLymph node-resident dendritic cellsHSV-specific T cellsCD4 T cell responsesNeedle injectionHerpes simplex virus 1 (HSV-1) infectionSimplex virus 1 infectionT cell primingT cell responsesVirus-1 infectionMode of infectionDC populationsCell primingVaginal infectionsImmune responseMucosal tissuesMucosal surfacesHSV-1Cell responses
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
2007
Vaginal epithelial dendritic cells renew from bone marrow precursors
Iijima N, Linehan MM, Saeland S, Iwasaki A. Vaginal epithelial dendritic cells renew from bone marrow precursors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 19061-19066. PMID: 18006657, PMCID: PMC2141908, DOI: 10.1073/pnas.0707179104.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAnimals, CongenicAntigens, CDAntigens, SurfaceBone Marrow CellsCell LineageDiestrusEpidermal CellsEpithelial CellsFemaleHerpes GenitalisLectins, C-TypeLymph NodesMannose-Binding LectinsMiceMice, Inbred C57BLMice, TransgenicMucous MembraneMultipotent Stem CellsOrgan SpecificityRadiation ChimeraVaginaConceptsEpithelial dendritic cellsDendritic cellsLangerhans cellsKey professional antigen-presenting cellsProfessional antigen-presenting cellsSkin Langerhans cellsAntigen-presenting cellsPrimary immune responseEpidermal Langerhans cellsMucosal epithelial liningBone marrow precursorsSquamous epithelial layerStratified squamous epithelial layerHSV-2Sex hormonesImmune responseOral cavityVaginal mucosaEpithelial liningMarrow precursorsActivation statusSpecialized subsetCytometric analysisEpithelial layerCells
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 defenseA crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide
Shen H, Iwasaki A. A crucial role for plasmacytoid dendritic cells in antiviral protection by CpG ODN–based vaginal microbicide. Journal Of Clinical Investigation 2006, 116: 2237-2243. PMID: 16878177, PMCID: PMC1518794, DOI: 10.1172/jci28681.Peer-Reviewed Original ResearchConceptsCpG ODNPlasmacytoid DCsHerpes simplex virus type 2Simplex virus type 2Lethal vaginal challengeVaginal stromal cellsPlasmacytoid dendritic cellsGenital herpes infectionIFN-alphabeta receptorAssociated inflammatory responseVirus type 2Vaginal challengeDendritic cellsHerpes infectionTLR agonistsMicrobicide efficacyTopical microbicidesVaginal microbicidesInflammatory responseI IFNAntiviral protectionType 2Antiviral genesStromal compartmentVaginal application
2004
In 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
Vaginal 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
2002
Expression of DC-SIGN by Dendritic Cells of Intestinal and Genital Mucosae in Humans and Rhesus Macaques
Jameson B, Baribaud F, Pöhlmann S, Ghavimi D, Mortari F, Doms RW, Iwasaki A. Expression of DC-SIGN by Dendritic Cells of Intestinal and Genital Mucosae in Humans and Rhesus Macaques. Journal Of Virology 2002, 76: 1866-1875. PMID: 11799181, PMCID: PMC135921, DOI: 10.1128/jvi.76.4.1866-1875.2002.Peer-Reviewed Original ResearchConceptsDC-SIGN expressionDendritic cellsDC-SIGNHuman immunodeficiency virus (HIV) transmissionRhesus macaquesDC-SIGNR expressionDistinct DC populationsSolitary lymphoid nodulesSubepithelial dendritic cellsSubepithelial dome regionTriple colour analysisPlasmacytoid dendritic cellsVirus transmissionDC-SIGNRIntact vaginal mucosaSpecific ICAM-3DC populationsHIV coreceptorsGenital mucosaLangerhans cellsPeyer's patchesGenital tractTerminal ileumInterfollicular regionsVaginal epithelium