2024
Beyond antiviral: role of IFN-I in brain development
Baker C, Iwasaki A. Beyond antiviral: role of IFN-I in brain development. Trends In Immunology 2024, 45: 322-324. PMID: 38644134, DOI: 10.1016/j.it.2024.04.004.Commentaries, Editorials and LettersMeSH KeywordsAnimalsBrainHumansInterferon Type IMiceMicrogliaNeuronal PlasticityNeuronsPhagocytosisSignal Transduction
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 efficacyKDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeThe 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
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 diseaseMiceType I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19
Park A, Iwasaki A. Type I and Type III Interferons – Induction, Signaling, Evasion, and Application to Combat COVID-19. Cell Host & Microbe 2020, 27: 870-878. PMID: 32464097, PMCID: PMC7255347, DOI: 10.1016/j.chom.2020.05.008.Peer-Reviewed Original ResearchConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Syndrome coronavirus 2Role of interferonType ICoronavirus disease 2019COVID-19Innate antiviral responseOngoing global threatCoronavirus 2Pathogenic coronavirusesTreatment strategiesDisease 2019Protective effectHuman coronavirusesRecombinant interferonMERS-CoVSARS-CoVAntiviral responseInterferonAntiviral therapeuticsCombat COVID-19Interferon inductionGlobal pandemic
2019
Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice
Pi R, Iwasaki A, Sewald X, Mothes W, Uchil PD. Murine Leukemia Virus Exploits Innate Sensing by Toll-Like Receptor 7 in B-1 Cells To Establish Infection and Locally Spread in Mice. Journal Of Virology 2019, 93: 10.1128/jvi.00930-19. PMID: 31434732, PMCID: PMC6803250, DOI: 10.1128/jvi.00930-19.Peer-Reviewed Original ResearchConceptsPopliteal lymph nodesFriend murine leukemia virusInnate immune sensing pathwaysToll-like receptor 7Viral spreadMurine leukemia virusCell-deficient miceType I interferon responseWild-type miceCell populationsType I interferonLeukemia virusRobust virus replicationI interferon responseAntiviral intervention strategiesInfected cell typesSentinel macrophagesAdoptive transferCell typesLymph nodesReceptor 7Virus infectionInnate sensingB cellsI interferon
2018
The interaction between IKKα and LC3 promotes type I interferon production through the TLR9-containing LAPosome
Hayashi K, Taura M, Iwasaki A. The interaction between IKKα and LC3 promotes type I interferon production through the TLR9-containing LAPosome. Science Signaling 2018, 11 PMID: 29717061, PMCID: PMC6462218, DOI: 10.1126/scisignal.aan4144.Peer-Reviewed Original ResearchConceptsInterferon regulatory factor 7Autophagy protein LC3Type I IFN productionI interferonI IFN productionMicrotubule-associated proteinsPutative LC3Type I interferon productionEndosomal vesiclesAutophagosome formationNoncanonical autophagyToll-like receptor 9Production of IFNStimulation of TLR9Regulatory factor 7Protein LC3Direct bindingI interferon productionIFN productionEndosomesChain 3Type I interferonKinase IKKαLC3Lap formationType I interferons instigate fetal demise after Zika virus infection
Yockey LJ, Jurado KA, Arora N, Millet A, Rakib T, Milano KM, Hastings AK, Fikrig E, Kong Y, Horvath TL, Weatherbee S, Kliman HJ, Coyne CB, Iwasaki A. Type I interferons instigate fetal demise after Zika virus infection. Science Immunology 2018, 3 PMID: 29305462, PMCID: PMC6049088, DOI: 10.1126/sciimmunol.aao1680.Peer-Reviewed Original ResearchConceptsZika virus infectionZIKV infectionI IFNsI interferonType I interferonGrowth restrictionFetal demiseVirus infectionSevere fetal growth restrictionType I IFNsChorionic villous explantsAdverse fetal outcomesCongenital viral infectionFetal growth restrictionMaternal-fetal barrierType IFunctional type IPlacental damageFetal outcomesPregnancy complicationsEarly pregnancyFetal resorptionZIKV diseasePregnant damsSpontaneous abortion
2017
B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice
Gibb DR, Liu J, Santhanakrishnan M, Natarajan P, Madrid DJ, Patel S, Eisenbarth SC, Tormey CA, Stowell SR, Iwasaki A, Hendrickson JE. B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice. Transfusion 2017, 57: 2595-2608. PMID: 28836263, PMCID: PMC5745367, DOI: 10.1111/trf.14288.Peer-Reviewed Original ResearchConceptsBone marrow chimeric miceHuman KEL glycoproteinType 1 interferonB cellsMean fluorescence intensityChimeric miceRed blood cell antigensBlood cell antigensGerminal center B cellsWT B cellsRBC alloimmunizationIgG alloantibodiesAlloimmune responseB cell differentiationRed blood cellsTransfusion protocolControl miceInflammatory stateWT miceAutoimmune pathologyIgG productionIFNAR1 expressionPlasma cellsAntiviral immunityInflammatory stimuliType 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 receptors
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
Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity
Hayashi K, Sasai M, Iwasaki A. Toll-like receptor 9 trafficking and signaling for type I interferons requires PIKfyve activity. International Immunology 2015, 27: 435-445. PMID: 25925170, PMCID: PMC4560039, DOI: 10.1093/intimm/dxv021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCell MembraneDendritic CellsDNA-Binding ProteinsEndosomesInterferon Type ILysosome-Associated Membrane GlycoproteinsMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesProtein TransportSignal TransductionToll-Like Receptor 7Toll-Like Receptor 9Transcription FactorsVesicle-Associated Membrane Protein 3ConceptsDifferent dendritic cell subsetsIFN inductionDendritic cell subsetsInduction of cytokinesType I IFN inductionType I IFNType I interferonI IFN inductionViral nucleic acidsAnti-viral programsTLR9 traffickingCell subsetsTLR9 signalsI IFNI interferonInhibitor treatmentDistinct subcellular membranesRAW264.7 cellsType I interferon (IFN) genesTLR9Distinct endosomal compartmentsInterferon genesTLR traffickingConfocal microscopyInductionMitochondrial DNA stress primes the antiviral innate immune response
West AP, Khoury-Hanold W, Staron M, Tal MC, Pineda CM, Lang SM, Bestwick M, Duguay BA, Raimundo N, MacDuff DA, Kaech SM, Smiley JR, Means RE, Iwasaki A, Shadel GS. Mitochondrial DNA stress primes the antiviral innate immune response. Nature 2015, 520: 553-557. PMID: 25642965, PMCID: PMC4409480, DOI: 10.1038/nature14156.Peer-Reviewed Original Research
2014
Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA
Rongvaux A, Jackson R, Harman CC, Li T, West AP, de Zoete MR, Wu Y, Yordy B, Lakhani SA, Kuan CY, Taniguchi T, Shadel GS, Chen ZJ, Iwasaki A, Flavell RA. Apoptotic Caspases Prevent the Induction of Type I Interferons by Mitochondrial DNA. Cell 2014, 159: 1563-1577. PMID: 25525875, PMCID: PMC4272443, DOI: 10.1016/j.cell.2014.11.037.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCaspasesDNA, MitochondrialInflammationInterferon Type IMiceMice, KnockoutSignal TransductionVirus DiseasesConceptsMitochondrial outer membrane permeabilizationCell deathOuter membrane permeabilizationType I interferonDNA-dependent activationCaspase-dependent mannerI interferonCGAS/STING pathwayMitochondrial DNAApoptotic caspasesMembrane permeabilizationActive caspasesProapoptotic caspasesMitochondriaCaspasesSTING pathwayIFN responseAntiviral immunityCentral roleDual controlPathwayProinflammatory typeInductionCellsActivation
2013
Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts
Mattei LM, Cotmore SF, Tattersall P, Iwasaki A. Parvovirus evades interferon-dependent viral control in primary mouse embryonic fibroblasts. Virology 2013, 442: 20-27. PMID: 23676303, PMCID: PMC3767977, DOI: 10.1016/j.virol.2013.03.020.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonIFN responseAntiviral immune mechanismsType I interferonInnate defense mechanismsMouse embryonic fibroblastsMVMp infectionViral controlImmune mechanismsInnate sensingAntiviral programViral replicationViral sensorsMurine parvovirusPoly (I:C) stimulationVirusEmbryonic fibroblastsType IMiceDefense mechanismsMinute virusMVMpPrimary mouse embryonic fibroblasts
2012
Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes
Henault J, Martinez J, Riggs JM, Tian J, Mehta P, Clarke L, Sasai M, Latz E, Brinkmann MM, Iwasaki A, Coyle AJ, Kolbeck R, Green DR, Sanjuan MA. Noncanonical Autophagy Is Required for Type I Interferon Secretion in Response to DNA-Immune Complexes. Immunity 2012, 37: 986-997. PMID: 23219390, PMCID: PMC3786711, DOI: 10.1016/j.immuni.2012.09.014.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Adaptor protein 3Plasmacytoid dendritic cellsDNA-containing immune complexesI interferonPathogenic DNAMicrotubule-associated proteinsType I interferon secretionIFN-α productionDNA immune complexesPreinitiation complexType I interferonAnti-DNA autoantibodiesNoncanonical autophagyAutophagic pathwayHost DNADendritic cellsAutoimmune disordersReceptor 9Interferon secretionChain 3Immune complexesProtein 3DNAInterferonA Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus
Yordy B, Iijima N, Huttner A, Leib D, Iwasaki A. A Neuron-Specific Role for Autophagy in Antiviral Defense against Herpes Simplex Virus. Cell Host & Microbe 2012, 12: 334-345. PMID: 22980330, PMCID: PMC3454454, DOI: 10.1016/j.chom.2012.07.013.Peer-Reviewed Original ResearchConceptsI interferonHSV-1 replicationDorsal root ganglionic neuronsType I IFN treatmentHerpes simplex type 1I IFN treatmentI IFNsHSV-1 infectionHerpes simplex virusNeuron-specific rolesSimplex type 1Type I interferonMucosal epithelial cellsDRG neuronsGanglionic neuronsNeurotropic virusesIFN treatmentSimplex virusViral infectionAntiviral pathwaysViral replicationType 1Antiviral strategiesLittle type INeurons
2010
Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3
Sasai M, Linehan MM, Iwasaki A. Bifurcation of Toll-Like Receptor 9 Signaling by Adaptor Protein 3. Science 2010, 329: 1530-1534. PMID: 20847273, PMCID: PMC3063333, DOI: 10.1126/science.1187029.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Protein Complex 3Adaptor Protein Complex beta SubunitsAnimalsCells, CulturedCytokinesCytoplasmic VesiclesDendritic CellsEndosomesInterferon Regulatory Factor-7Interferon Type ILysosomal-Associated Membrane Protein 2MacrophagesMembrane Transport ProteinsMiceMice, Inbred C57BLMyeloid Differentiation Factor 88OligodeoxyribonucleotidesProtein TransportRecombinant Fusion ProteinsSignal TransductionTNF Receptor-Associated Factor 3Toll-Like Receptor 9Transcriptional ActivationVesicle-Associated Membrane Protein 3ConceptsI interferonTLR9 signalsEndosomal Toll-like receptors 7Toll-like receptor 9 signalingToll-like receptor 7Protein 3Type I IFNsDependent proinflammatory cytokinesInterferon regulatory factor 7I IFNsProinflammatory cytokine genesType I interferonNuclear factor κBRegulatory factor 7Viral nucleic acidsProinflammatory cytokinesReceptor 7Factor κBCytokine genesTLR9Adaptor protein 3Intracellular mechanismsFactor 7Viral pathogensReceptor traffickingCD8+ 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