2023
Mature B cells and mesenchymal stem cells control emergency myelopoiesis
Lim V, Feng X, Miao R, Zehentmeier S, Ewing-Crystal N, Lee M, Tumanov A, Oh J, Iwasaki A, Wang A, Choi J, Pereira J. Mature B cells and mesenchymal stem cells control emergency myelopoiesis. Life Science Alliance 2023, 6: e202301924. PMID: 36717247, PMCID: PMC9889502, DOI: 10.26508/lsa.202301924.Peer-Reviewed Original ResearchConceptsMarrow mesenchymal stem cellsSystemic inflammationMature B cellsB cellsEmergency myelopoiesisMesenchymal stem cellsIL-1 receptorBone marrow mesenchymal stem cellsStem cellsMyeloid cell productionMonocyte numbersB lineage cellsCCL2 productionViral infectionLymphotoxin α1β2InflammationReduced survivalLymphopoietic activityMyelopoiesisLymphopoiesisImportant regulatorLTβRCell productionCellsGenetic blockingPD-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
Lack 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
A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice
Mao T, Israelow B, Lucas C, Vogels CBF, Gomez-Calvo ML, Fedorova O, Breban MI, Menasche BL, Dong H, Linehan M, Alpert T, Anderson F, Earnest R, Fauver J, Kalinich C, Munyenyembe K, Ott I, Petrone M, Rothman J, Watkins A, Wilen C, Landry M, Grubaugh N, Pyle A, Iwasaki A. A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice. Journal Of Experimental Medicine 2021, 219: e20211818. PMID: 34757384, PMCID: PMC8590200, DOI: 10.1084/jem.20211818.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionChronic SARS-CoV-2 infectionVariants of concernLethal SARS-CoV-2 infectionPost-infection therapyLower respiratory tractPost-exposure treatmentType I interferonSARS-CoV-2Effective medical countermeasuresAdaptive immune systemBroad-spectrum antiviralsContext of infectionSingle doseRespiratory tractViral controlImmunodeficient miceSevere diseaseMouse modelI interferonViral infectionImmune systemInnate immunityDisease preventionConsiderable efficacyThe first 12 months of COVID-19: a timeline of immunological insights
Carvalho T, Krammer F, Iwasaki A. The first 12 months of COVID-19: a timeline of immunological insights. Nature Reviews Immunology 2021, 21: 245-256. PMID: 33723416, PMCID: PMC7958099, DOI: 10.1038/s41577-021-00522-1.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2Antibodies, ViralAutoantibodiesCOVID-19COVID-19 Drug TreatmentCOVID-19 SerotherapyCOVID-19 VaccinesDexamethasoneDrug DevelopmentGlucocorticoidsHumansImmunization, PassiveImmunologic FactorsInterferon Type IReceptors, CoronavirusSARS-CoV-2Systemic Inflammatory Response SyndromeConceptsSARS-CoV-2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Numerous candidate vaccinesSyndrome coronavirus 2Coronavirus disease 2019Peer-reviewed journalsCandidate vaccinesCoronavirus 2Pneumonia casesDisease 2019Immune responseViral infectionImmunological insightsNovel coronavirusInitial reportCOVID-19First yearMonthsHighlight gapsPreprint serversUnidentified originFuture investigationsVaccineInfection
2020
Contributions of maternal and fetal antiviral immunity in congenital disease
Yockey LJ, Lucas C, Iwasaki A. Contributions of maternal and fetal antiviral immunity in congenital disease. Science 2020, 368: 608-612. PMID: 32381717, DOI: 10.1126/science.aaz1960.Peer-Reviewed Original ResearchConceptsViral infectionCongenital diseaseDirect viral toxicityMaternal immune responseMaternal immune activationFetal developmental defectsFuture treatment strategiesImmune defense mechanismsPregnancy outcomesFetal demiseImmune activationUncontrolled inflammationMaternal healthChronic infectionTreatment strategiesImmune responseAntiviral immunityRange of syndromesFetal developmentTissue damagePathological effectsInfectionViral toxicityDevastating consequencesPregnancySeasonality of Respiratory Viral Infections
Moriyama M, Hugentobler WJ, Iwasaki A. Seasonality of Respiratory Viral Infections. Annual Review Of Virology 2020, 7: 1-19. PMID: 32196426, DOI: 10.1146/annurev-virology-012420-022445.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusCoronavirus InfectionsCOVID-19HumansHumidityInfectious Disease Incubation PeriodInfluenza, HumanOrthomyxoviridaePandemicsPicornaviridae InfectionsPneumonia, ViralRespiratory Tract InfectionsRhinovirusSARS-CoV-2SeasonsSevere Acute Respiratory SyndromeSevere acute respiratory syndrome-related coronavirusSeverity of Illness IndexTemperatureConceptsRespiratory viral infectionsViral infectionSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral respiratory infectionsAdaptive immune responsesRespiratory viral diseasesRespiratory infectionsRespiratory virusesInfluenza diseaseRespiratory tractImmune responseAnnual epidemicsHost responseInfectionMajor contributing factorViral diseasesDiseaseContributing factorVirus stabilityVirusEpidemicRecent studiesYearsHuman population
2019
Low ambient humidity impairs barrier function and innate resistance against influenza infection
Kudo E, Song E, Yockey LJ, Rakib T, Wong PW, Homer RJ, Iwasaki A. Low ambient humidity impairs barrier function and innate resistance against influenza infection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 10905-10910. PMID: 31085641, PMCID: PMC6561219, DOI: 10.1073/pnas.1902840116.Peer-Reviewed Original ResearchConceptsInfluenza infectionImpair barrier functionImpairs host defenseSeasonal influenza virusesInfluenza virus infectionLungs of miceImpairs mucociliary clearanceTissue repairInduction of IFNInnate antiviral defenseViral burdenMucociliary clearanceDisease outcomeRespiratory challengeVirus infectionSevere diseaseViral infectionCongenic miceHost responseViral transmissionHost defenseSingle-cell RNA sequencingInnate resistanceDisease pathologyInfluenza virus
2018
An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication
Orzalli MH, Smith A, Jurado KA, Iwasaki A, Garlick JA, Kagan JC. An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus Replication. Molecular Cell 2018, 71: 825-840.e6. PMID: 30100266, PMCID: PMC6411291, DOI: 10.1016/j.molcel.2018.07.009.Peer-Reviewed Original ResearchConceptsDamage-associated molecular patternsIL-1Host-derived damage-associated molecular patternsViral replicationVirus replicationInfected cellsInterleukin-1 family cytokinesIL-1 Signaling PathwayInflammatory gene expressionIL-1 actsHuman skin explantsProtective immunityIL-1αBarrier defenseInflammatory signalsViral infectionFamily cytokinesSkin explantsGene expressionMolecular patternsSkin fibroblastsSignaling pathwaysAntiviral systemBarrier epitheliaCell typesTopical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner
Gopinath S, Kim MV, Rakib T, Wong PW, van Zandt M, Barry NA, Kaisho T, Goodman AL, Iwasaki A. Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner. Nature Microbiology 2018, 3: 611-621. PMID: 29632368, PMCID: PMC5918160, DOI: 10.1038/s41564-018-0138-2.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, TopicalAminoglycosidesAnimalsAnti-Bacterial AgentsDisease Models, AnimalGene Expression ProfilingGene Expression RegulationGerm-Free LifeHumansInfluenza A virusMiceMicrobiotaOligonucleotide Array Sequence AnalysisSimplexvirusToll-Like Receptor 3Transcription FactorsVirus DiseasesVirus ReplicationZika VirusConceptsToll-like receptor 3Aminoglycoside treatmentInterferon-stimulated genesViral infectionReceptor 3ISG inductionAminoglycoside antibioticsMicrobiota-independent mannerGerm-free miceAdapter-inducing interferonInterferon regulatory factor 3Herpes simplex virusTopical mucosal applicationRegulatory factor 3Dendritic cellsAntibiotic useAntiviral effectAminoglycoside applicationHost resistanceSimplex virusAntiviral resistanceVaginal mucosaMarked upregulationMucosal applicationTopical application
2017
Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice
Gibb DR, Liu J, Natarajan P, Santhanakrishnan M, Madrid DJ, Eisenbarth SC, Zimring JC, Iwasaki A, Hendrickson JE. Type I IFN Is Necessary and Sufficient for Inflammation-Induced Red Blood Cell Alloimmunization in Mice. The Journal Of Immunology 2017, 199: 1041-1050. PMID: 28630094, PMCID: PMC5568771, DOI: 10.4049/jimmunol.1700401.Peer-Reviewed Original ResearchConceptsRBC alloimmunizationRed blood cell alloimmunizationCertain inflammatory disordersCompatible blood productsProduction of alloantibodiesHemolytic transfusion reactionsCytosolic pattern recognition receptorsType I IFNsTransgenic murine modelType I IFNPattern recognition receptorsTransfusion protocolAlloimmune responseRBC transfusionInflammatory disordersInflammatory conditionsTransfusion reactionsBlood productsInflammatory stimuliMurine modelI IFNsAlloimmunizationI IFNViral infectionRecognition receptorsIRE1α promotes viral infection by conferring resistance to apoptosis
Fink SL, Jayewickreme TR, Molony RD, Iwawaki T, Landis CS, Lindenbach BD, Iwasaki A. IRE1α promotes viral infection by conferring resistance to apoptosis. Science Signaling 2017, 10 PMID: 28588082, PMCID: PMC5535312, DOI: 10.1126/scisignal.aai7814.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCase-Control StudiesCells, CulturedEndoribonucleasesFemaleHepacivirusHepatitis CHerpes SimplexHumansLiverMaleMiceMice, KnockoutMicroRNAsProtein Serine-Threonine KinasesSimplexvirusVesicular StomatitisVesicular stomatitis Indiana virusViral Nonstructural ProteinsVirus ReplicationX-Box Binding Protein 1ConceptsX-box binding protein 1Type I IFN responseI IFN responseUnfolded protein responseViral-induced apoptosisActivation of IRE1αLiver biopsyAntiviral therapyHealthy controlsAntiviral resistanceViral infectionBinding protein 1Antiapoptotic Bcl-2 familyIFN responseViral replicationDeficient cellsProtein 1Apoptosis resistancePossible targetsProsurvival roleEnzyme 1αApoptosisInfectionIntrinsic pathwayType I
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 IInfectionO-linked sugars sound the alarm
Gopinath S, Kumamoto Y, Iwasaki A. O-linked sugars sound the alarm. Nature Immunology 2016, 17: 119-120. PMID: 26784258, DOI: 10.1038/ni.3364.Peer-Reviewed Original ResearchAutophagy Snuffs a Macrophage’s Inner Fire
Khoury-Hanold W, Iwasaki A. Autophagy Snuffs a Macrophage’s Inner Fire. Cell Host & Microbe 2016, 19: 9-11. PMID: 26764592, DOI: 10.1016/j.chom.2015.12.015.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
2013
Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response
Sellers SL, Iwasaki A, Payne GW. Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response. PLOS ONE 2013, 8: e60741. PMID: 23573281, PMCID: PMC3616017, DOI: 10.1371/journal.pone.0060741.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsArteriolesCell DegranulationChlorocebus aethiopsFemaleHerpes SimplexLymph NodesMast CellsMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNifedipineNitric OxideNitric Oxide Synthase Type IIIPhenylephrineTumor Necrosis Factor-alphaVasoconstrictionVasodilator AgentsVero CellsConceptsAdaptive immune responsesEndothelial nitric oxide synthaseImmune responseVascular remodelingHerpes simplex type II infectionT cell-dependent mechanismGenetic ablation modelCell-dependent mechanismNitric oxide levelsType II infectionNitric oxide synthaseCourse of infectionInguinal LNsLN cellularityVascular eventsVascular changesArteriole diameterPharmacological blockadeMain arterioleOxide synthaseTNFα expressionMast cellsOxide levelsViral infectionIntravital microscopyCell type-dependent requirement of autophagy in HSV-1 antiviral defense
Yordy B, Iwasaki A. Cell type-dependent requirement of autophagy in HSV-1 antiviral defense. Autophagy 2013, 9: 236-238. PMID: 23095715, PMCID: PMC3552887, DOI: 10.4161/auto.22506.Peer-Reviewed Original ResearchConceptsDRG neuronsAntiviral programI interferonHSV-1Dorsal root ganglion neuronsRobust type I IFN responseType I IFN responseMost viral infectionsAntiviral immune mechanismsAntiviral defenseHSV-1 infectionI IFN responseType I interferonInnate antiviral responseType IGanglion neuronsImmune mechanismsViral controlLess cell deathViral infectionAntiviral responseIFN responseInfection modelAntiviral defense mechanismNeurons
2012
A Virological View of Innate Immune Recognition
Iwasaki A. A Virological View of Innate Immune Recognition. Annual Review Of Microbiology 2012, 66: 177-196. PMID: 22994491, PMCID: PMC3549330, DOI: 10.1146/annurev-micro-092611-150203.Peer-Reviewed Original Research