2024
SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity
Peña-Hernández M, Alfajaro M, Filler R, Moriyama M, Keeler E, Ranglin Z, Kong Y, Mao T, Menasche B, Mankowski M, Zhao Z, Vogels C, Hahn A, Kalinich C, Zhang S, Huston N, Wan H, Araujo-Tavares R, Lindenbach B, Homer R, Pyle A, Martinez D, Grubaugh N, Israelow B, Iwasaki A, Wilen C. SARS-CoV-2-related bat viruses evade human intrinsic immunity but lack efficient transmission capacity. Nature Microbiology 2024, 9: 2038-2050. PMID: 39075235, DOI: 10.1038/s41564-024-01765-z.Peer-Reviewed Original ResearchBat coronavirusesRelatives of SARS-CoV-2Upper airwayUpper airways of miceEpithelial cellsHuman nasal epithelial cellsAirways of miceMajor histocompatibility complex class I.SARS-CoV-2Nasal epithelial cellsHistocompatibility complex class I.Human bronchial epithelial cellsGenetic similarityBronchial epithelial cellsInnate immune restrictionCoronavirus replicationFunctional characterizationMolecular cloningReduced pathogenesisImpaired replicationBat virusCoronavirus pathogenesisPandemic potentialHigh-risk familiesImmune restriction
2018
Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus
Mihaylova VT, Kong Y, Fedorova O, Sharma L, Dela Cruz CS, Pyle AM, Iwasaki A, Foxman EF. Regional Differences in Airway Epithelial Cells Reveal Tradeoff between Defense against Oxidative Stress and Defense against Rhinovirus. Cell Reports 2018, 24: 3000-3007.e3. PMID: 30208323, PMCID: PMC6190718, DOI: 10.1016/j.celrep.2018.08.033.Peer-Reviewed Original ResearchConceptsRIG-I stimulationAntiviral responseRhinovirus infectionBronchial airway epithelial cellsAcute respiratory infectionsEpithelial cellsRobust antiviral responseAirway epithelial cellsPrimary human nasalAirway damageRespiratory infectionsAirway microenvironmentAsthma attacksNasal mucosaLeading causeNrf2 knockdownNasal cellsNrf2 activationHuman nasalEpithelial defenseHost defenseBronchial cellsInfectionOxidative stressRhinovirus
2017
Zika virus causes testicular atrophy
Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ, Hastings AK, Homer RJ, Iwasaki A, Fikrig E. Zika virus causes testicular atrophy. Science Advances 2017, 3: e1602899. PMID: 28261663, PMCID: PMC5321463, DOI: 10.1126/sciadv.1602899.Peer-Reviewed Original ResearchConceptsZika virusTesticular atrophyAcute viremic phaseZIKV-infected miceMosquito-borne flavivirusTestosterone-producing Leydig cellsProgressive testicular atrophyZIKV persistenceFetal infectionViremic phaseNeonatal abnormalitiesSerum testosteroneZIKV infectionNeurological dysfunctionSubcutaneous injectionZIKV replicationLeydig cellsVirus replicationVertical transmissionEpithelial cellsMiceViral RNAReproductive deficienciesAtrophyMale fertility
2016
Early local immune defences in the respiratory tract
Iwasaki A, Foxman EF, Molony RD. Early local immune defences in the respiratory tract. Nature Reviews Immunology 2016, 17: 7-20. PMID: 27890913, PMCID: PMC5480291, DOI: 10.1038/nri.2016.117.Peer-Reviewed Original ResearchConceptsRespiratory tractImmune responseDendritic cellsType 2 immune responsesType 1 immune responsePlasmacytoid dendritic cellsEpithelial cellsTissue-resident lymphocytesLower respiratory tractType of infectionUpper respiratory tractAirway epithelial cellsLocal immune defensePattern recognition receptorsAntimicrobial host defenseLymphoid cell typesCell typesRespiratory infectionsEffector cellsSecrete cytokinesAllergen resultsInnate sensorsMast cellsAirway cellsPathological inflammationTwo interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature
Foxman EF, Storer JA, Vanaja K, Levchenko A, Iwasaki A. Two interferon-independent double-stranded RNA-induced host defense strategies suppress the common cold virus at warm temperature. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 8496-8501. PMID: 27402752, PMCID: PMC4968739, DOI: 10.1073/pnas.1601942113.Peer-Reviewed Original ResearchConceptsIFN-independent mechanismsEpithelial cellsHost defense strategiesHost cell deathIFN inductionHuman bronchial epithelial cellsReduced virus productionCommon cold virusInfected epithelial cellsB-cell lymphoma 2 (Bcl-2) overexpressionBronchial epithelial cellsDiverse stimuliViral replicationAntiviral pathwaysCell deathH1-HeLa cellsTemperature-dependent replicationCell typesSingle replication cycleTemperature-dependent growthReplication cycleWarmer temperaturesCool temperaturesDefense strategiesType 1 IFN responseViral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality
Khoury-Hanold W, Yordy B, Kong P, Kong Y, Ge W, Szigeti-Buck K, Ralevski A, Horvath TL, Iwasaki A. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. Cell Host & Microbe 2016, 19: 788-799. PMID: 27281569, PMCID: PMC4902295, DOI: 10.1016/j.chom.2016.05.008.Peer-Reviewed Original ResearchConceptsGenital HSV-1 infectionEnteric nervous systemHSV-1 infectionSensory nervous systemNervous systemGenital herpesToxic megacolonHSV-1Genital mucosal epithelial cellsPeripheral sensory nervous systemDorsal root gangliaPathological inflammatory responsesMucosal epithelial cellsHerpes simplex virus 1Simplex virus 1Urinary retentionEnteric neuronsLaxative treatmentAutonomic gangliaRoot gangliaInflammatory responseViral gene transcriptionMouse modelInfectionEpithelial cells
2007
Mucosal Dendritic Cells
Iwasaki A. Mucosal Dendritic Cells. Annual Review Of Immunology 2007, 25: 381-418. PMID: 17378762, DOI: 10.1146/annurev.immunol.25.022106.141634.Peer-Reviewed Original ResearchConceptsMucosal dendritic cellsDendritic cellsMucosal surfacesSpecialized dendritic cellsRobust protective immunityAdaptive immune systemMucus-secreting cellsProtective immunityEnvironmental antigensMucosal barrierCommensal floraImmune systemEpithelial cellsRecognition of microorganismsAntigenAppropriate local responsesCellsVital functionsResponsePathogensAbsence of pathogensExcretionImmunity
2004
Involvement of Dendritic Cell Subsets in the Induction of Oral Tolerance and Immunity
FLEETON M, CONTRACTOR N, LEON F, HE J, WETZEL D, DERMODY T, IWASAKI A, KELSALL B. Involvement of Dendritic Cell Subsets in the Induction of Oral Tolerance and Immunity. Annals Of The New York Academy Of Sciences 2004, 1029: 60-65. PMID: 15681744, DOI: 10.1196/annals.1309.008.Peer-Reviewed Original ResearchConceptsSubepithelial dome regionDendritic cellsApoptotic epithelial cellsDC maturationEpithelial cellsOral administrationT cellsImmune responsePP follicle-associated epitheliumSystemic antiviral immune responsesDendritic cell subsetsPlasmacytoid dendritic cellsCross-present antigensRegulatory T cellsInduction of immunityB cell responsesAntiviral immune responseActive viral infectionFollicle-associated epitheliumMurine Peyer's patchesDC infectionDC subsetsOral antigenDC populationsOral tolerance