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 ResearchMeSH KeywordsAnimalsDiet, KetogenicInfluenza A virusMiceMice, Inbred C57BLMice, KnockoutOrthomyxoviridae InfectionsT-LymphocytesConceptsΓδ 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 adaptationLow 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
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 immunityMx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
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 ResearchMeSH KeywordsAnimalsHumansImmunity, InnateOrthomyxoviridaeOrthomyxoviridae InfectionsReceptors, Pattern RecognitionConceptsInfluenza 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
Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I
Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 13910-13915. PMID: 23918369, PMCID: PMC3752242, DOI: 10.1073/pnas.1303275110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBronchoalveolar Lavage FluidCytokinesDEAD Box Protein 58DEAD-box RNA HelicasesFlow CytometryHistological TechniquesImmunity, InnateImmunohistochemistryInfluenza A virusMembrane GlycoproteinsMiceMice, Inbred C57BLOrthomyxoviridae InfectionsRespiratory Tract InfectionsSignal TransductionToll-Like Receptor 7Viral LoadVirus ReplicationConceptsToll-like receptor 7Innate immune responseRespiratory tractInfected wild-type miceHost innate immune responseAirways of miceViral target cellsWild-type miceAcid-inducible gene 1RIG-I pathwayPattern recognition receptorsHost innate defenseViral replication efficiencyInflammatory mediatorsBronchoalveolar lavageViral loadProinflammatory programProinflammatory responseReceptor 7IAV infectionInflammatory responseVirus infectionLow doseViral replicationVirus replicationIL-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
Influenza virus activates inflammasomes via its intracellular M2 ion channel
Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nature Immunology 2010, 11: 404-410. PMID: 20383149, PMCID: PMC2857582, DOI: 10.1038/ni.1861.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCells, CulturedCytokinesDendritic CellsGenetic EngineeringGolgi ApparatusHydrogen-Ion ConcentrationIon ChannelsMacrophagesMembrane GlycoproteinsMiceMice, Inbred C57BLMice, KnockoutMonensinNLR Family, Pyrin Domain-Containing 3 ProteinOncogene Proteins, ViralOrthomyxoviridaeOrthomyxoviridae InfectionsPotassium ChlorideProtein TransportProtonsSequence DeletionToll-Like Receptor 7Viral Matrix ProteinsVirus Replication
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
1999
Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization
Iwasaki A, Dela Cruz C, Young A, Barber B. Epitope-specific cytotoxic T lymphocyte induction by minigene DNA immunization. Vaccine 1999, 17: 2081-2088. PMID: 10217610, DOI: 10.1016/s0264-410x(98)00411-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, ViralAntigen PresentationBiolisticsCytokinesEpitopes, T-LymphocyteFemaleGenes, ViralHistocompatibility Antigens Class IInjections, IntramuscularMiceMice, Inbred StrainsNucleocapsid ProteinsNucleoproteinsOrthomyxoviridaeOrthomyxoviridae InfectionsPeptide FragmentsPlasmidsProtein Sorting SignalsRecombinant ProteinsRNA-Binding ProteinsT-Lymphocytes, CytotoxicTumor Cells, CulturedVaccines, DNAViral Core ProteinsConceptsCTL responsesCytotoxic T lymphocyte inductionEpitope-specific CTL responsesT lymphocyte responsesT lymphocyte inductionPlasmid DNA vaccineFull-length antigenLymphocyte responsesIL-12Lymphocyte inductionAntibody responseDNA immunizationDNA vaccineGene gun bombardmentPotent antibodiesGM-CSFCytokine combinationsNeedle injectionInfluenza virusSkeletal muscleSkin epidermisNucleoproteinMinimal effectResponseImmunization