2021
Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes
Ravindra NG, Alfajaro MM, Gasque V, Huston NC, Wan H, Szigeti-Buck K, Yasumoto Y, Greaney AM, Habet V, Chow RD, Chen JS, Wei J, Filler RB, Wang B, Wang G, Niklason LE, Montgomery RR, Eisenbarth SC, Chen S, Williams A, Iwasaki A, Horvath TL, Foxman EF, Pierce RW, Pyle AM, van Dijk D, Wilen CB. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLOS Biology 2021, 19: e3001143. PMID: 33730024, PMCID: PMC8007021, DOI: 10.1371/journal.pbio.3001143.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionSARS-CoV-2Human bronchial epithelial cellsInterferon-stimulated genesCell state changesAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSyndrome coronavirus 2 infectionCell tropismCoronavirus 2 infectionCoronavirus disease 2019Onset of infectionCell-intrinsic expressionCourse of infectionAir-liquid interface culturesHost-viral interactionsBronchial epithelial cellsSingle-cell RNA sequencingCell typesIL-1Disease 2019Human airwaysDevelopment of therapeuticsDrug AdministrationViral replication
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
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 types
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 response
2014
Epigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth
Ding S, Khoury-Hanold W, Iwasaki A, Robek MD. Epigenetic Reprogramming of the Type III Interferon Response Potentiates Antiviral Activity and Suppresses Tumor Growth. PLOS Biology 2014, 12: e1001758. PMID: 24409098, PMCID: PMC3883642, DOI: 10.1371/journal.pbio.1001758.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell Line, TumorCell ProliferationCpG IslandsCricetinaeCytomegalovirusDNA MethylationEpigenesis, GeneticHepatocytesHerpesvirus 1, HumanHistone Deacetylase InhibitorsHistone DeacetylasesHost-Pathogen InteractionsHumansInterferon-gammaMiceNIH 3T3 CellsOrgan SpecificityPromoter Regions, GeneticReceptors, CytokineReceptors, InterferonRNA, Small InterferingSignal TransductionVesiculovirusConceptsHDAC inhibitorsPro-apoptotic activityRepression machineryExpression programsTranscriptional silencingEpigenetic reprogrammingEpigenetic rewiringUbiquitous expressionMolecular mechanismsCell typesSpecific mannerSuppress tumor growthReceptor subunitsPotential antitumor strategyNonresponsive cellsIFN responseAntiviral immunityViral pathogensExpressionReceptor expressionType III interferonsAntitumor strategyΒ receptorTumor growthEpithelial origin
2012
MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Hoshi N, Schenten D, Nish SA, Walther Z, Gagliani N, Flavell RA, Reizis B, Shen Z, Fox JG, Iwasaki A, Medzhitov R. MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice. Nature Communications 2012, 3: 1120. PMID: 23047678, PMCID: PMC3521499, DOI: 10.1038/ncomms2113.Peer-Reviewed Original ResearchConceptsToll-like receptorsInterleukin-10Mononuclear phagocytesIL-10-deficient miceT helper 17 responsesColonic mononuclear phagocytesDevelopment of colitisInflammatory bowel diseaseColitis developmentBowel diseaseInterleukin-23MyD88 expressionInterleukin-1βInterleukin-6Intestinal homeostasisEpithelial expressionMyD88Multiple cell typesMiceCell typesReceptorsPhagocytesBacterial sensingDistinct populationsHigh levels
2007
Innate control of adaptive immunity: Dendritic cells and beyond
Lee HK, Iwasaki A. Innate control of adaptive immunity: Dendritic cells and beyond. Seminars In Immunology 2007, 19: 48-55. PMID: 17276695, DOI: 10.1016/j.smim.2006.12.001.Peer-Reviewed Original ResearchConceptsDendritic cellsAdaptive immune responsesImmune responseInnate immune recognitionKey cell typesCell typesEffector cellsNaïve lymphocytesAdaptive immunityInnate controlImmune recognitionAnatomical locationImmediate defensePathogen triggersCellsRecent understandingLymphocytesInfectionImmunityResponse