2020
Commensal Microbiota Modulation of Natural Resistance to Virus Infection
Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal Microbiota Modulation of Natural Resistance to Virus Infection. Cell 2020, 183: 1312-1324.e10. PMID: 33212011, PMCID: PMC7799371, DOI: 10.1016/j.cell.2020.10.047.Peer-Reviewed Original ResearchConceptsMicrobial moleculesVesicular stomatitis virusCommensal microbesSpecific commensal microbesInduction of IFNVirus infectionNatural resistanceOuter membraneGut commensal microbesIFN-β expressionImmune system regulationHuman diseasesPhysiological importanceInduces expressionSource of IFNMicrobesHomeostatic conditionsStomatitis virusIFN-IsMicrobiota modulationAntiviral immunityCrucial mediatorIFNPolysaccharide AAntiviral activityContributions 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 consequencesPregnancy
2018
Topical 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
Immune Regulation of Antibody Access to Neuronal Tissues
Iwasaki A. Immune Regulation of Antibody Access to Neuronal Tissues. Trends In Molecular Medicine 2017, 23: 227-245. PMID: 28185790, PMCID: PMC5626569, DOI: 10.1016/j.molmed.2017.01.004.Peer-Reviewed Original ResearchConceptsBlood-brain barrierBlood-nerve barrierAdaptive immune systemImmune systemAntibody accessInnate immune controlUse of vaccinesImmune controlNeurotropic virusesCancer immunotherapyImmune regulationImmune surveillanceT cellsTAM receptorsNeurodegenerative conditionsAlzheimer's diseaseNeuronal tissueNeural tissueDiseaseTissueNovel insightsSuch novel insightsImmunotherapyCD4Cells
2016
Exploiting Mucosal Immunity for Antiviral Vaccines
Iwasaki A. Exploiting Mucosal Immunity for Antiviral Vaccines. Annual Review Of Immunology 2016, 34: 575-608. PMID: 27168245, DOI: 10.1146/annurev-immunol-032414-112315.Peer-Reviewed Original ResearchConceptsMucosal immunityHuman immunodeficiency virusEffective immune protectionHost immune responseHerpes simplex virusImmunodeficiency virusMucosal vaccinesImmune protectionSuccessful vaccineImmune responseSimplex virusAntiviral vaccinesMucosal surfacesVaccine developmentVaccine designInfluenza virusFirst lineVaccineViral pathogensImmunityViral diseasesVirusDangerous pathogensPathogensDiseaseO-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 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
Tissue‐resident memory T cells
Shin H, Iwasaki A. Tissue‐resident memory T cells. Immunological Reviews 2013, 255: 165-181. PMID: 23947354, PMCID: PMC3748618, DOI: 10.1111/imr.12087.Peer-Reviewed Original ResearchConceptsMemory T cellsHuman immunodeficiency virusHerpes simplex virusGenital tractT cellsPeripheral tissuesImmune systemTissue-resident memory T cellsMemory T cell migrationTissue-resident memory cellsT cell-based vaccinesMemory T cell populationsMemory T cell subsetsAntibody-based vaccinesT cell recruitmentT cell subsetsNew vaccination strategiesT cell populationsSecondary lymphoid organsNon-lymphoid tissuesPortal of entryT cell migrationAdaptive immune systemTRM cellsEffector memory
2012
Autophagy and selective deployment of Atg proteins in antiviral defense
Yordy B, Tal MC, Hayashi K, Arojo O, Iwasaki A. Autophagy and selective deployment of Atg proteins in antiviral defense. International Immunology 2012, 25: 1-10. PMID: 23042773, PMCID: PMC3534236, DOI: 10.1093/intimm/dxs101.Peer-Reviewed Original ResearchConceptsAutophagy machineryAtg proteinsAntiviral defenseViral pathogen-associated molecular patternsPathogen-associated molecular patternsEukaryotic cellsCellular homeostasisCanonical autophagyViral replication sitesMajor histocompatibility complex presentationIntracellular transportAntiviral proteinCytosolic componentsRegulatory functionsEndolysosomal compartmentsReplication sitesAutophagyMachineryMolecular patternsDiverse repertoireIntracellular materialProteinToll-like receptorsViral antigen processingSelective targetingUnique features of antiviral immune system of the vaginal mucosa
Kumamoto Y, Iwasaki A. Unique features of antiviral immune system of the vaginal mucosa. Current Opinion In Immunology 2012, 24: 411-416. PMID: 22673876, PMCID: PMC3423557, DOI: 10.1016/j.coi.2012.05.006.Peer-Reviewed Original ResearchConceptsVaginal mucosaVirus-specific CD4Development of vaccinesAntiviral immune systemHuman papillomavirusGenital tractT cellsImmune responseAdaptive immunityHuman vaccinesMucosal organsImmune systemVaccineAntiviral defenseMucosaVaginaVirusRecent studiesWide spectrumVast majorityCurrent understandingCD8CD4PapillomavirusImmunobiology
2011
Control of antiviral immunity by pattern recognition and the microbiome
Pang IK, Iwasaki A. Control of antiviral immunity by pattern recognition and the microbiome. Immunological Reviews 2011, 245: 209-226. PMID: 22168422, PMCID: PMC3659816, DOI: 10.1111/j.1600-065x.2011.01073.x.Peer-Reviewed Original ResearchConceptsAdaptive immunityInnate pattern recognition receptorsChronic viral infectionsAdaptive immune responsesExtra-intestinal infectionsHost immune systemPattern recognition receptorsTransduce signalsImmune activationAutoimmune diseasesProbiotic therapyMammalian hostsImmune responseAntiviral immunityViral infectionMucosal surfacesViral recognitionImmune systemInvasive microbesProper developmentMicrobial sensingResident microbiotaInnate defenseSuch diseasesHost susceptibilityAutophagy in the control and pathogenesis of viral infection
Yordy B, Iwasaki A. Autophagy in the control and pathogenesis of viral infection. Current Opinion In Virology 2011, 1: 196-203. PMID: 21927636, PMCID: PMC3171969, DOI: 10.1016/j.coviro.2011.05.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutophagyHumansImmunity, InnateVirus DiseasesVirus Physiological PhenomenaVirusesConceptsEukaryotic defense mechanismEukaryotic cell metabolismIntracellular pathogensVertebrate immune systemTime of starvationConstitutive autophagyCellular proteinsKey unanswered questionsCell metabolismAncient abilityAutophagyDefense mechanismsCell processesAntiviral immune responseRecent findingsPathogensCentral roleViral pathogensImmune systemOrganellesViral infectionMachineryUnanswered questionsImmune responseProteinMitoxosome: a mitochondrial platform for cross‐talk between cellular stress and antiviral signaling
Tal MC, Iwasaki A. Mitoxosome: a mitochondrial platform for cross‐talk between cellular stress and antiviral signaling. Immunological Reviews 2011, 243: 215-234. PMID: 21884179, PMCID: PMC3170140, DOI: 10.1111/j.1600-065x.2011.01038.x.Peer-Reviewed Original ResearchConceptsCellular stressMitochondrial functionCell biologic analysesViral recognitionInnate immune signalingDynamic relocalizationAntiviral signalingImmune signalingMitochondriaAntiviral responseMultiple pathwaysAntiviral immunityCurrent understandingRecent findingsSignalingViral replicationInnate responseIntegrated viewBiologic analysisRecent studiesSignalosomeRelocalizationKey componentStressIntegral platformGenome–virome interactions: examining the role of common viral infections in complex disease
Foxman EF, Iwasaki A. Genome–virome interactions: examining the role of common viral infections in complex disease. Nature Reviews Microbiology 2011, 9: 254-264. PMID: 21407242, PMCID: PMC3678363, DOI: 10.1038/nrmicro2541.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesAssociation studiesHuman genetic variationLarge regulatory networkHost-virus interactionsCrohn's diseaseRegulatory networksHost genesGenetic variationModel hostGenomic technologiesAutophagy pathwayAntiviral defenseViral infectionAdditional host factorsEnvironmental conditionsComplex diseasesCommon viral infectionsCases of asthmaSubsequent disease developmentGenesHostHost factorsDisease developmentParticular virus
2010
Regulation of Adaptive Immunity by the Innate Immune System
Iwasaki A, Medzhitov R. Regulation of Adaptive Immunity by the Innate Immune System. Science 2010, 327: 291-295. PMID: 20075244, PMCID: PMC3645875, DOI: 10.1126/science.1183021.Peer-Reviewed Original ResearchConceptsInnate immune recognitionB lymphocyte-mediated immune responsesImmune responsePattern recognition receptorsImmune recognitionAntigen-specific adaptive immune responsesLymphocyte-mediated immune responsesMicrobial pathogensInnate immune systemAdaptive immune responsesRecognition receptorsHost defenseField of immunologyAdaptive immunityImmune systemFundamental questionsReceptorsRegulationPathwayPathogensInvasionDefenseInjuryInfectionDiscovery
2009
Autophagy and Innate Recognition Systems
Tal MC, Iwasaki A. Autophagy and Innate Recognition Systems. Current Topics In Microbiology And Immunology 2009, 335: 107-121. PMID: 19802562, DOI: 10.1007/978-3-642-00302-8_5.Peer-Reviewed Original ResearchConceptsAutophagic machineryInnate immune systemDouble-membrane structureViral replication complexProcess of autophagyImportant physiological processesInduction of autophagyInnate recognition systemsCellular homeostasisReplication complexPattern recognition receptorsAutophagy pathwayLysosomal degradationPhysiological processesCytosolic constituentsEfficient phagocytosisInnate pattern recognition receptorsRNA virusesAutophagyCytosolic sensorsKey moleculesExtracellular pathogensRecognition receptorsImmune systemViral sensorsInflammasomes in viral infection
Ichinohe T, Iwasaki A. Inflammasomes in viral infection. VIRUS - Beiträge Zur Sozialgeschichte Der Medizin 2009, 59: 13. PMID: 19927984, DOI: 10.2222/jsv.59.13.Peer-Reviewed Original ResearchConceptsNOD-like receptorsProinflammatory cytokine interleukin-1betaRole of inflammasomesInfluenza virus infectionCytokine interleukin-1betaInnate immune responseCaspase-1 activationIL-33IL-18NLRP3 inflammasomeVirus infectionImmune responseInterleukin-1betaAdaptive immunityInflammasome activationMicrobial motifsDamage-associated signalsViral infectionInflammasomeMultiprotein complexesAdaptor proteinInfectionCertain virusesCell deathIntracellular sensors
2008
Autophagy and antiviral immunity
Lee HK, Iwasaki A. Autophagy and antiviral immunity. Current Opinion In Immunology 2008, 20: 23-29. PMID: 18262399, PMCID: PMC2271118, DOI: 10.1016/j.coi.2008.01.001.Peer-Reviewed Original ResearchConceptsViral infectionViral replicationAdaptive antiviral immune responsesEndogenous viral antigensCD4 T cellsMHC class II loading compartmentsAntiviral immune responseCritical effector mechanismAdaptive immune systemViral antigensEffector mechanismsT cellsImmune responseAntiviral immunityImmune systemLoading compartmentCertain virusesInfectionAutophagyRecent studiesCellsAntigenImmunityCellular homeostasis
2007
Toll-like receptors regulation of viral infection and disease
Thompson JM, Iwasaki A. Toll-like receptors regulation of viral infection and disease. Advanced Drug Delivery Reviews 2007, 60: 786-794. PMID: 18280610, PMCID: PMC2410298, DOI: 10.1016/j.addr.2007.11.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHost-Pathogen InteractionsHumansReceptors, VirusToll-Like ReceptorsVirus DiseasesVirusesConceptsToll-like receptorsVirus infectionRole of TLRsProtective anti-viral immunityToll-like receptor regulationAdaptive immune responsesAnti-viral immunityMammalian Toll-like receptorsVirus-induced diseaseViral nucleic acidsStudies of miceTLR activationInteraction of virusImmune responseViral infectionTLR systemTLR proteinsReceptor regulationInfectionDiseaseOutcomesCritical roleMiceImmunityReceptors