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
2022
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2021
A humanized mouse model of chronic COVID-19
Sefik E, Israelow B, Mirza H, Zhao J, Qu R, Kaffe E, Song E, Halene S, Meffre E, Kluger Y, Nussenzweig M, Wilen CB, Iwasaki A, Flavell RA. A humanized mouse model of chronic COVID-19. Nature Biotechnology 2021, 40: 906-920. PMID: 34921308, PMCID: PMC9203605, DOI: 10.1038/s41587-021-01155-4.Peer-Reviewed Original ResearchConceptsChronic COVID-19Humanized mouse modelImmune responseMouse modelAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCOVID-19Adaptive human immune responsesInterferon-stimulated gene signaturePersistent viral RNACoronavirus 2 infectionPatient-derived antibodiesT-cell lymphopeniaHuman immune responseHyperactive immune responseCoronavirus disease 2019Inflammatory macrophage responseImmunological injuryLung pathologyCell lymphopeniaDisease 2019Severe diseaseRodent modelsInflammatory macrophagesIntranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protection
2020
Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling
Israelow B, Song E, Mao T, Lu P, Meir A, Liu F, Alfajaro MM, Wei J, Dong H, Homer RJ, Ring A, Wilen CB, Iwasaki A. Mouse model of SARS-CoV-2 reveals inflammatory role of type I interferon signaling. Journal Of Experimental Medicine 2020, 217: e20201241. PMID: 32750141, PMCID: PMC7401025, DOI: 10.1084/jem.20201241.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsBetacoronavirusCell Line, TumorCoronavirus InfectionsCOVID-19DependovirusDisease Models, AnimalFemaleHumansInflammationInterferon Type ILungMaleMiceMice, Inbred C57BLMice, TransgenicPandemicsParvoviridae InfectionsPeptidyl-Dipeptidase APneumonia, ViralSARS-CoV-2Signal TransductionVirus ReplicationConceptsSARS-CoV-2Type I interferonMouse modelI interferonRobust SARS-CoV-2 infectionSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2SARS-CoV-2 replicationCOVID-19 patientsSyndrome coronavirus 2Patient-derived virusesSignificant fatality ratePathological findingsInflammatory rolePathological responseEnzyme 2Receptor angiotensinFatality rateVaccine developmentGenetic backgroundViral replicationCoronavirus diseaseMice
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
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
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 cells