2023
PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses
Mao T, Israelow B, Peña-Hernández MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, Iwasaki A. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022, 378: eabo2523. PMID: 36302057, PMCID: PMC9798903, DOI: 10.1126/science.abo2523.Peer-Reviewed Original ResearchConceptsRespiratory mucosaSystemic immunityLethal SARS-CoV-2 infectionAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicSARS-CoV-2 infectionProtective mucosal immunityCross-reactive immunityT cell responsesCoronavirus 2 pandemicPrimary vaccinationParenteral vaccinesMucosal immunityVaccine strategiesRespiratory tractImmunoglobulin AMemory BImmune memoryPartial immunityCell responsesPoor immunityImmunitySpike proteinMucosaVaccineMultiscale PHATE identifies multimodal signatures of COVID-19
Kuchroo M, Huang J, Wong P, Grenier JC, Shung D, Tong A, Lucas C, Klein J, Burkhardt DB, Gigante S, Godavarthi A, Rieck B, Israelow B, Simonov M, Mao T, Oh JE, Silva J, Takahashi T, Odio CD, Casanovas-Massana A, Fournier J, Farhadian S, Dela Cruz C, Ko A, Hirn M, Wilson F, Hussin J, Wolf G, Iwasaki A, Krishnaswamy S. Multiscale PHATE identifies multimodal signatures of COVID-19. Nature Biotechnology 2022, 40: 681-691. PMID: 35228707, PMCID: PMC10015653, DOI: 10.1038/s41587-021-01186-x.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingTransposase-accessible chromatinSingle-cell sequencingRNA sequencingBiological insightsPopulation groupingsSophisticated computational toolsBiological featuresSequencingFlow cytometryComputational toolsChromatinBiomedical communityDifferent data typesCell responsesCellsPhateLack of association between pandemic chilblains and SARS-CoV-2 infection
Gehlhausen JR, Little AJ, Ko CJ, Emmenegger M, Lucas C, Wong P, Klein J, Lu P, Mao T, Jaycox J, Wang E, Ugwu N, Muenker C, Mekael D, Klein R, Patrignelli R, Antaya R, McNiff J, Damsky W, Kamath K, Shon J, Ring A, Yildirim I, Omer S, Ko A, Aguzzi A, Iwasaki A, Obaid A, Lu-Culligan A, Nelson A, Brito A, Nunez A, Martin A, Watkins A, Geng B, Kalinich C, Harden C, Todeasa C, Jensen C, Kim D, McDonald D, Shepard D, Courchaine E, White E, Song E, Silva E, Kudo E, DeIuliis G, Rahming H, Park H, Matos I, Nouws J, Valdez J, Fauver J, Lim J, Rose K, Anastasio K, Brower K, Glick L, Sharma L, Sewanan L, Knaggs L, Minasyan M, Batsu M, Petrone M, Kuang M, Nakahata M, Campbell M, Linehan M, Askenase M, Simonov M, Smolgovsky M, Sonnert N, Naushad N, Vijayakumar P, Martinello R, Datta R, Handoko R, Bermejo S, Prophet S, Bickerton S, Velazquez S, Alpert T, Rice T, Khoury-Hanold W, Peng X, Yang Y, Cao Y, Strong Y. Lack of association between pandemic chilblains and SARS-CoV-2 infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2122090119. PMID: 35217624, PMCID: PMC8892496, DOI: 10.1073/pnas.2122090119.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionPrior SARS-CoV-2 infectionSARS-CoV-2PC biopsiesAcute respiratory syndrome coronavirus 2 pandemicSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemicT-cell receptor sequencingCell receptor sequencingT cell responsesCoronavirus 2 pandemicEnzyme-linked immunosorbent assayLack of associationCOVID toesSkin eruptionAntibody responseImmunohistochemistry studiesBackground seroprevalenceTissue microarrayViral infectionStimulation assaysCell responsesInfectionChilblainsImmunosorbent assayAbortive infectionHigh-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Chen JS, Chow RD, Song E, Mao T, Israelow B, Kamath K, Bozekowski J, Haynes WA, Filler RB, Menasche BL, Wei J, Alfajaro MM, Song W, Peng L, Carter L, Weinstein JS, Gowthaman U, Chen S, Craft J, Shon JC, Iwasaki A, Wilen CB, Eisenbarth SC. High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells. Science Immunology 2022, 7: eabl5652. PMID: 34914544, PMCID: PMC8977051, DOI: 10.1126/sciimmunol.abl5652.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Follicular helper cellsB cell responsesHelper cellsAntibody productionCell responsesSARS-CoV-2 vaccinationB-cell receptor sequencingSevere COVID-19Cell receptor sequencingIndependent antibodiesT cell-B cell interactionsViral inflammationAntiviral antibodiesImmunoglobulin class switchingVirus infectionGerminal centersViral infectionClonal repertoireInfectionAntibodiesClass switchingCOVID-19Patients
2021
Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Lucas C, Vogels CBF, Yildirim I, Rothman JE, Lu P, Monteiro V, Gehlhausen JR, Campbell M, Silva J, Tabachnikova A, Peña-Hernandez MA, Muenker MC, Breban MI, Fauver JR, Mohanty S, Huang J, Shaw A, Ko A, Omer S, Grubaugh N, Iwasaki A. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature 2021, 600: 523-529. PMID: 34634791, PMCID: PMC9348899, DOI: 10.1038/s41586-021-04085-y.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 variantsMRNA vaccine-induced immunityT-cell activation markersSARS-CoV-2 antibodiesSecond vaccine doseVaccine-induced immunityCell activation markersT cell responsesHigh antibody titresSARS-CoV-2Vaccine boosterVaccine doseActivation markersVaccine dosesHumoral immunityAntibody titresMRNA vaccinesVitro stimulationNeutralization capacityNeutralization responseCell responsesE484KNucleocapsid peptideAntibody-binding sitesGreater reductionKynurenic acid may underlie sex-specific immune responses to COVID-19
Cai Y, Kim DJ, Takahashi T, Broadhurst DI, Yan H, Ma S, Rattray NJW, Casanovas-Massana A, Israelow B, Klein J, Lucas C, Mao T, Moore AJ, Muenker MC, Oh JE, Silva J, Wong P, team Y, Ko AI, Khan SA, Iwasaki A, Johnson CH. Kynurenic acid may underlie sex-specific immune responses to COVID-19. Science Signaling 2021, 14: eabf8483. PMID: 34230210, PMCID: PMC8432948, DOI: 10.1126/scisignal.abf8483.Peer-Reviewed Original ResearchConceptsKynurenic acidImmune responseClinical outcomesSex-specific immune responsesT cell responsesPoor clinical outcomeCOVID-19 patientsCoronavirus disease 2019COVID-19Sex-related differencesMale patientsCytokine abundanceInflammatory cytokinesKynurenine ratioSerum metabolomeDisease 2019Sex-specific linkKynurenine aminotransferaseCell responsesOld malePatientsMalesOutcomesResponseMetabolitesDivergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms
Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, Dandekar R, Loudermilk RP, Dai Y, Liu F, Sunshine S, Liu J, Wu W, Hawes IA, Alvarenga BD, Huynh T, McAlpine L, Rahman NT, Geng B, Chiarella J, Goldman-Israelow B, Vogels CBF, Grubaugh ND, Casanovas-Massana A, Phinney BS, Salemi M, Alexander JR, Gallego JA, Lencz T, Walsh H, Wapniarski AE, Mohanty S, Lucas C, Klein J, Mao T, Oh J, Ring A, Spudich S, Ko AI, Kleinstein SH, Pak J, DeRisi JL, Iwasaki A, Pleasure SJ, Wilson MR, Farhadian SF. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Reports Medicine 2021, 2: 100288. PMID: 33969321, PMCID: PMC8091032, DOI: 10.1016/j.xcrm.2021.100288.Peer-Reviewed Original ResearchNeurological symptomsImmune responseCerebrospinal fluidAnti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodiesCOVID-19Self-reactive immune responsesSARS-CoV-2 antibodiesCompartmentalized immune responseCSF immunoglobulin GRole of autoimmunityCOVID-19 patientsB cell responsesCoronavirus disease 2019Immune surveyNeurologic sequelaePulmonary infectionBrain infectionSerum antibodiesDisease 2019Monoclonal antibody targetsAnimal modelsTarget epitopesCell activationCell responsesSingle-cell RNA sequencing
2019
Ketogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg EL, Molony RD, Kudo E, Sidorov S, Kong Y, Dixit VD, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. Science Immunology 2019, 4 PMID: 31732517, PMCID: PMC7189564, DOI: 10.1126/sciimmunol.aav2026.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietIAV infectionT cellsGlobal health care concernHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionHealth care concernHigh-carbohydrate dietInfluenza diseaseKD feedingVirus infectionNew therapiesAntiviral resistanceHepatic ketogenesisCare concernsCell responsesInfectionBarrier functionDietMetabolic adaptationKetogenic diet activates protective γδ T cell responses against influenza virus infection
Goldberg E, Molony R, Sidorov S, Kudo E, Dixit V, Iwasaki A. Ketogenic diet activates protective γδ T cell responses against influenza virus infection. The Journal Of Immunology 2019, 202: 62.7-62.7. DOI: 10.4049/jimmunol.202.supp.62.7.Peer-Reviewed Original ResearchΓδ T cellsKetogenic dietIAV infectionT cellsHigh-fat high-carbohydrate dietHigh-fat ketogenic dietΓδ T cell responsesInfection-associated morbidityLethal IAV infectionT cell responsesInfluenza virus infectionAnti-viral resistanceHigh-carbohydrate dietInfluenza diseaseKD feedingNovel therapiesVirus infectionGlobal healthcare concernHepatic ketogenesisAbstract InfluenzaCell responsesHealthcare concernInfectionBarrier functionDiet
2017
RAB15 empowers dendritic cells to drive antiviral immunity
Wong P, Iwasaki A. RAB15 empowers dendritic cells to drive antiviral immunity. Science Immunology 2017, 2: eaan6448. PMID: 28783705, DOI: 10.1126/sciimmunol.aan6448.Peer-Reviewed Original Research
2015
Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation
Kashem SW, Igyártó B, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, Drummond RA, Zurawski SM, Zurawski G, Berman J, Iwasaki A, Brown GD, Kaplan DH. Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity 2015, 42: 356-366. PMID: 25680275, PMCID: PMC4343045, DOI: 10.1016/j.immuni.2015.01.008.Peer-Reviewed Original ResearchConceptsT helper cell responsesHelper cell responsesCell responsesInterleukin-6Systemic infectionDectin-1 ligationTh1 cell responsesTh cell responsesT helper 17 (Th17) cell differentiationT helper cell differentiationTissue-specific protectionSkin infection modelMurine skin infection modelC. albicansHelper cell differentiationMucocutaneous immunityCutaneous infectionsVaccine strategiesLangerhans cellsSystemic immunityT cellsCell differentiationInfection modelInfectionImmunity
2014
Innate immunity to influenza virus infection
Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nature Reviews Immunology 2014, 14: 315-328. PMID: 24762827, PMCID: PMC4104278, DOI: 10.1038/nri3665.Peer-Reviewed Original ResearchConceptsInfluenza virus infectionToll-like receptor 7T cell responsesVirus infectionInterferon-stimulated genesIL-1βNLRP3 inflammasomeViral challengeB cellsCell responsesHigh-dose viral challengeInfluenza virusAntiviral B cellsMultiple pattern recognition receptorsPlasmacytoid dendritic cellsAdaptive immune responsesInfected cellsRetinoic acid-inducible gene IAirway epithelial cellsAcid-inducible gene IPattern recognition receptorsInfluenza virus-infected cellsVirus-infected cellsAntiviral defense genesDendritic cells
2013
IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus
Pang IK, Ichinohe T, Iwasaki A. IL-1R signaling in dendritic cells replaces pattern-recognition receptors in promoting CD8+ T cell responses to influenza A virus. Nature Immunology 2013, 14: 246-253. PMID: 23314004, PMCID: PMC3577947, DOI: 10.1038/ni.2514.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell DifferentiationCell MovementDendritic CellsInfluenza A virusInterleukin-1Lymphocyte ActivationMembrane GlycoproteinsMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMyeloid Differentiation Factor 88Nerve Tissue ProteinsOrthomyxoviridae InfectionsReceptors, CCR7Receptors, Cell SurfaceReceptors, Interleukin-1Receptors, Pattern RecognitionSignal TransductionToll-Like Receptor 7
2010
CD8+ T Cell Responses following Replication-Defective Adenovirus Serotype 5 Immunization Are Dependent on CD11c+ Dendritic Cells but Show Redundancy in Their Requirement of TLR and Nucleotide-Binding Oligomerization Domain-Like Receptor Signaling
Lindsay RW, Darrah PA, Quinn KM, Wille-Reece U, Mattei LM, Iwasaki A, Kasturi SP, Pulendran B, Gall JG, Spies AG, Seder RA. CD8+ T Cell Responses following Replication-Defective Adenovirus Serotype 5 Immunization Are Dependent on CD11c+ Dendritic Cells but Show Redundancy in Their Requirement of TLR and Nucleotide-Binding Oligomerization Domain-Like Receptor Signaling. The Journal Of Immunology 2010, 185: 1513-1521. PMID: 20610651, DOI: 10.4049/jimmunol.1000338.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviruses, HumanAnimalsAntigen PresentationCD11c AntigenCD8-Positive T-LymphocytesDefective VirusesDendritic CellsImmunity, InnateImmunophenotypingInterferon Type IInterleukin-12Intracellular Signaling Peptides and ProteinsLymph NodesMiceMice, Inbred C57BLMice, KnockoutOligodeoxyribonucleotidesSignal TransductionToll-Like ReceptorsViral VaccinesVirionConceptsT cell responsesCD8 T cell responsesDendritic cellsCell responsesRAd5 immunizationCD8 responsesDC subsetsInnate cytokinesOligomerization domain-like receptor protein 3Domain-like receptor protein 3OT-I CD8 T cellsCD4 T cell responsesCD8 T cell proliferationNucleotide-Binding Oligomerization DomainReplication-defective adenovirus serotype 5Plasmacytoid dendritic cellsReceptor protein 3CD8 T cellsDistinct DC subsetsT cell immunityApoptosis-associated speck-like proteinPre-existing immunityT cell proliferationLike receptor signalingType I IFN
2009
Differential 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
In vivo requirement for autophagy in antigen presentation by dendritic cells
LEE H, Lee Y, Chervonsky A, Mizushima N, Iwasaki A. In vivo requirement for autophagy in antigen presentation by dendritic cells. The FASEB Journal 2008, 22: 1068.13-1068.13. DOI: 10.1096/fasebj.22.1_supplement.1068.13.Peer-Reviewed Original ResearchCD4 T cellsCD4 T cell responsesT cell responsesDendritic cellsAntigen presentationT cellsMajor histocompatibility complexCell responsesFetal liver chimeric miceClass II major histocompatibility complexLiver chimeric miceDegradation of antigenMHC II moleculesPresentation of antigensDendritic cell abilityConditional knockout miceMHC-II complexesCD11c-CreRole of autophagyMHC-IIKnockout miceChimeric miceCytosolic antigensVivo requirementAntigen
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 cells
1999
I. Mucosal dendritic cells: their specialized role in initiating T cell responses*
Iwasaki A, Kelsall B. I. Mucosal dendritic cells: their specialized role in initiating T cell responses*. American Journal Of Physiology 1999, 276: g1074-g1078. PMID: 10329996, DOI: 10.1152/ajpgi.1999.276.5.g1074.Peer-Reviewed Original ResearchConceptsT cell responsesMucosal dendritic cellsDendritic cellsCell responsesCompetent antigen-presenting cellsPrimary T cell responsesTissue-resident dendritic cellsResident dendritic cellsAntigen-presenting cellsDC populationsLymphoid tissueRecent studiesCellsFunctional studiesResponseMucosaIsolation procedureSpecialized role