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
Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination
Suberi A, Grun M, Mao T, Israelow B, Reschke M, Grundler J, Akhtar L, Lee T, Shin K, Piotrowski-Daspit A, Homer R, Iwasaki A, Suh H, Saltzman W. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination. Science Translational Medicine 2023, 15: eabq0603. PMID: 37585505, PMCID: PMC11137749, DOI: 10.1126/scitranslmed.abq0603.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Lethal viral challengeAntigen-presenting cellsSyndrome coronavirus 2Humoral adaptive immunityLung-targeting deliveryIntranasal vaccinationMucosal vaccinationPulmonary diseaseMucosal vaccinesSusceptible miceCoronavirus 2Viral challengeAdaptive immunityLungTranslational potentialMessenger RNA (mRNA) therapeuticsVaccinationMRNADeliveryTherapeuticsRNA therapeuticsTherapeutic delivery
2021
Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, Iwasaki A. Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2. Science Immunology 2021, 6: eabl4509. PMID: 34623900, PMCID: PMC9047536, DOI: 10.1126/sciimmunol.abl4509.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Viral clearanceImmune determinantsMouse modelSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Cellular adaptive immunitySyndrome coronavirus 2Vivo protective capacityVariants of concernMRNA vaccinationHomologous infectionCellular immunityConvalescent miceCoronavirus 2Antibody responsePrimary infectionEffective vaccineAdaptive immunityConfer protectionInfectionNatural infectionProtective capacityClearance
2019
Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection
Vesely M, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N, Flavell RA. Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 2019, 178: 1176-1188.e15. PMID: 31442406, PMCID: PMC7057720, DOI: 10.1016/j.cell.2019.07.032.Peer-Reviewed Original ResearchConceptsCD4 TTissue-resident memory T cellsBacterial infectionsResident memory T cellsFunction of airwayLife-long protectionEffector memory TMemory T cellsTh17 cellsTRM cellsΓδ TEffector cellsMemory TBacterial clearanceT cellsIL-7Adaptive immunityMouse modelMemory responsesVaccine designHost defenseLymphatic endothelial cellsDepletion studiesEndothelial cellsCellular origin
2018
Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection
Lucas CGO, Kitoko JZ, Ferreira FM, Suzart VG, Papa MP, Coelho SVA, Cavazzoni CB, Paula-Neto HA, Olsen PC, Iwasaki A, Pereira RM, Pimentel-Coelho PM, Vale AM, de Arruda LB, Bozza MT. Critical role of CD4+ T cells and IFNγ signaling in antibody-mediated resistance to Zika virus infection. Nature Communications 2018, 9: 3136. PMID: 30087337, PMCID: PMC6081430, DOI: 10.1038/s41467-018-05519-4.Peer-Reviewed Original ResearchConceptsT cellsZika virusMurine adoptive transfer modelParticipation of CD4Adoptive transfer modelT cell responsesImportance of CD4Protective adaptive immunityRapid disease onsetZika virus infectionFuture vaccine designAntibody-mediated resistanceCytotoxic CD8Viral loadZIKV infectionAntibody responsePrimary infectionRecipient miceDisease onsetVirus infectionProtective effectAdaptive immunityIFNγ signalingCD4B lymphocytes
2016
AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity
Schmid ET, Pang IK, Silva E, Bosurgi L, Miner JJ, Diamond MS, Iwasaki A, Rothlin CV. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. ELife 2016, 5: e12414. PMID: 27350258, PMCID: PMC4924996, DOI: 10.7554/elife.12414.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonDendritic cellsIL-1βAntiviral T cell immunityAntiviral adaptive immunityPotent immunosuppressive functionT cell immunityT cell primingInhibition of AXLType I IFN receptorAxl receptor tyrosine kinaseReceptor tyrosine kinase AXLControl of infectionType I interferonI IFN receptorTyrosine kinase AXLDC maturationCell immunityWest Nile virusCell primingImmunosuppressive functionImmunosuppressive effectsAdaptive immunity
2015
Control of adaptive immunity by the innate immune system
Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system. Nature Immunology 2015, 16: 343-353. PMID: 25789684, PMCID: PMC4507498, DOI: 10.1038/ni.3123.Peer-Reviewed Original Research
2013
Innate immunity
Iwasaki A, Peiris M. Innate immunity. 2013, 267-282. DOI: 10.1002/9781118636817.ch17.Peer-Reviewed Original ResearchToll-like receptorsNOD-like receptorsImmune responseVirus infectionInfluenza virusHundreds of IFNProtective host responseInfluenza virus infectionAdaptive immune responsesInnate immune responseType I IFNInfluenza virus replicationInnate immune systemDendritic cellsNK cellsInfluenza infectionIL-1βInnate sensorsAdaptive immunityLike receptorsDetrimental pathologyI IFNAlveolar macrophagesHost responseImmune system
2012
Phagosome as the Organelle Linking Innate and Adaptive Immunity
Kagan JC, Iwasaki A. Phagosome as the Organelle Linking Innate and Adaptive Immunity. Traffic 2012, 13: 1053-1061. PMID: 22577865, PMCID: PMC3658133, DOI: 10.1111/j.1600-0854.2012.01377.x.Peer-Reviewed Original ResearchConceptsProcess of phagocytosisPhagosome traffickingAdaptive immunityAntimicrobial defense mechanismsDefinable unitSubcellular levelT cell-mediated immunityAdaptive immune systemDefense mechanismsToll-like receptorsPhagosomesPhagocytosisImmune systemImmunityMicrobesTraffickingAutophagyPathwayReceptorsInnateUnique 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
2011
Control of antiviral immunity by pattern recognition and the microbiome
Pang IK, Iwasaki A. Control of antiviral immunity by pattern recognition and the microbiome. Immunological Reviews 2011, 245: 209-226. PMID: 22168422, PMCID: PMC3659816, DOI: 10.1111/j.1600-065x.2011.01073.x.Peer-Reviewed Original ResearchConceptsAdaptive immunityInnate pattern recognition receptorsChronic viral infectionsAdaptive immune responsesExtra-intestinal infectionsHost immune systemPattern recognition receptorsTransduce signalsImmune activationAutoimmune diseasesProbiotic therapyMammalian hostsImmune responseAntiviral immunityViral infectionMucosal surfacesViral recognitionImmune systemInvasive microbesProper developmentMicrobial sensingResident microbiotaInnate defenseSuch diseasesHost susceptibility
2010
Antiviral immune responses in the genital tract: clues for vaccines
Iwasaki A. Antiviral immune responses in the genital tract: clues for vaccines. Nature Reviews Immunology 2010, 10: 699-711. PMID: 20829886, PMCID: PMC3678359, DOI: 10.1038/nri2836.Peer-Reviewed Original ResearchConceptsGenital mucosaT cellsGenital tractHerpes simplex virus type 2Simplex virus type 2Innate immune cellsT cell populationsAntiviral immune responseFemale genital tractPattern recognition receptorsVirus type 2Immune correlatesMemory CD4Memory CD8Viral clearanceHuman papillomavirusImmune cellsMemory lymphocytesSuccessful vaccineHIV-1Immune responseSevere diseaseVaginal epitheliumAdaptive immunityTarget cell typeRegulation of Adaptive Immunity by the Innate Immune System
Iwasaki A, Medzhitov R. Regulation of Adaptive Immunity by the Innate Immune System. Science 2010, 327: 291-295. PMID: 20075244, PMCID: PMC3645875, DOI: 10.1126/science.1183021.Peer-Reviewed Original ResearchConceptsInnate immune recognitionB lymphocyte-mediated immune responsesImmune responsePattern recognition receptorsImmune recognitionAntigen-specific adaptive immune responsesLymphocyte-mediated immune responsesMicrobial pathogensInnate immune systemAdaptive immune responsesRecognition receptorsHost defenseField of immunologyAdaptive immunityImmune systemFundamental questionsReceptorsRegulationPathwayPathogensInvasionDefenseInjuryInfectionDiscovery
2009
Inflammasome recognition of influenza virus is essential for adaptive immune responses
Ichinohe T, Lee HK, Ogura Y, Flavell R, Iwasaki A. Inflammasome recognition of influenza virus is essential for adaptive immune responses. Journal Of Experimental Medicine 2009, 206: 79-87. PMID: 19139171, PMCID: PMC2626661, DOI: 10.1084/jem.20081667.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody FormationApoptosis Regulatory ProteinsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1CD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell MovementCytoskeletal ProteinsDendritic CellsImmunity, CellularImmunity, InnateImmunoglobulin IsotypesInterleukin-1betaLungMacrophages, AlveolarMiceMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesNasal Lavage FluidNLR Family, Pyrin Domain-Containing 3 ProteinOrthomyxoviridaeOrthomyxoviridae InfectionsReceptors, Interleukin-1Survival AnalysisConceptsInfluenza virus infectionNOD-like receptorsInfluenza virusVirus infectionAdaptive immunityInflammasome activationRetinoic acid-inducible gene I.CD8 T cell responsesCaspase-1Influenza virus resultsMucosal IgA secretionProtective antiviral immunitySystemic IgG responseCD4 T cellsT cell responsesAdaptive immune responsesType I interferonInnate immune systemRespiratory infectionsIgG responsesProtective immunityTLR signalsIgA secretionReceptor 7T cellsInflammasomes in viral infection
Ichinohe T, Iwasaki A. Inflammasomes in viral infection. Uirusu 2009, 59: 13. PMID: 19927984, DOI: 10.2222/jsv.59.13.Peer-Reviewed Original ResearchConceptsNOD-like receptorsProinflammatory cytokine interleukin-1betaRole of inflammasomesInfluenza virus infectionCytokine interleukin-1betaInnate immune responseCaspase-1 activationIL-33IL-18NLRP3 inflammasomeVirus infectionImmune responseInterleukin-1betaAdaptive immunityInflammasome activationMicrobial motifsDamage-associated signalsViral infectionInflammasomeMultiprotein complexesAdaptor proteinInfectionCertain virusesCell deathIntracellular sensors
2008
Innate sensors of influenza virus: clues to developing better intranasal vaccines
Ichinohe T, Iwasaki A, Hasegawa H. Innate sensors of influenza virus: clues to developing better intranasal vaccines. Expert Review Of Vaccines 2008, 7: 1435-1445. PMID: 18980544, PMCID: PMC2724183, DOI: 10.1586/14760584.7.9.1435.Peer-Reviewed Original ResearchConceptsInfluenza vaccineInnate sensorsVirus infectionImmune systemInfluenza virusIntranasal influenza vaccineVariant virus infectionNatural infectionEffective influenza vaccinesInfluenza virus infectionToll-like receptorsRetinoic acid-inducible geneNOD-like receptorsInnate immune systemPattern recognition receptorsAdaptive immune systemAcid-inducible geneParenteral immunizationIntranasal vaccineMucosal immunitySystemic immunityInactivated vaccinesRespiratory tractAdaptive immunityLike receptorsDendritic cells and macrophages in the genitourinary tract
Iijima N, Thompson J, Iwasaki A. Dendritic cells and macrophages in the genitourinary tract. Mucosal Immunology 2008, 1: 451-459. PMID: 19079212, PMCID: PMC2684461, DOI: 10.1038/mi.2008.57.Peer-Reviewed Original ResearchConceptsAntigen-presenting cellsDendritic cellsGenitourinary tractGU tractUnderstanding of DCsSubsets of DCsImmune defenseFemale genital mucosaInnate immune defenseGenital mucosaMaternal toleranceSex hormonesAdaptive immunityReproductive functionMacrophagesTractNumerous agentsSTIsImportant reproductive functionsCellsDivergent rolesMucosaFetusesInfectionHormone
2007
Innate control of adaptive immunity: Dendritic cells and beyond
Lee HK, Iwasaki A. Innate control of adaptive immunity: Dendritic cells and beyond. Seminars In Immunology 2007, 19: 48-55. PMID: 17276695, DOI: 10.1016/j.smim.2006.12.001.Peer-Reviewed Original ResearchConceptsDendritic cellsAdaptive immune responsesImmune responseInnate immune recognitionKey cell typesCell typesEffector cellsNaïve lymphocytesAdaptive immunityInnate controlImmune recognitionAnatomical locationImmediate defensePathogen triggersCellsRecent understandingLymphocytesInfectionImmunityResponse
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
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