2023
Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity
Weizman O, Luyten S, Krykbaeva I, Song E, Mao T, Bosenberg M, Iwasaki A. Type 2 Dendritic Cells Orchestrate a Local Immune Circuit to Confer Antimetastatic Immunity. The Journal Of Immunology 2023, 210: 1146-1155. PMID: 36881866, PMCID: PMC10067787, DOI: 10.4049/jimmunol.2200697.Peer-Reviewed Original ResearchConceptsType 2 dendritic cellsMetastatic burdenImmune circuitsDendritic cellsConventional type 2 dendritic cellsSyngeneic murine melanomaNK cell compartmentImmune cell responsesColon cancer modelEarly metastatic seedingMetastatic controlTranscription factor IRF3DC populationsNK cellsProinflammatory cytokinesNucleic acid sensingPrimary tumorEffector responsesMetastatic spreadDisease outcomeIntracardiac injectionT cellsInitial immunityTissue-specific ablationCancer modelIL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii
Clark J, Weizman O, Aldridge D, Shallberg L, Eberhard J, Lanzar Z, Wasche D, Huck J, Zhou T, Ring A, Hunter C. IL-18BP mediates the balance between protective and pathological immune responses to Toxoplasma gondii. Cell Reports 2023, 42: 112147. PMID: 36827187, PMCID: PMC10131179, DOI: 10.1016/j.celrep.2023.112147.Peer-Reviewed Original ResearchConceptsInnate lymphoid cellsIL-18IL-18BPNatural killerToxoplasma gondiiIL-18 binding proteinEndogenous IL-18Exogenous IL-18Cell-mediated pathologyPathological immune responsesProduction of IFNAnti-pathogen responsesCell productionInterleukin-18Immune pathologyImmune responseLymphoid cellsCell responsesInnate resistanceCD4IFNGondiiInfectionPathologyLimited roleInfection induces tissue-resident memory NK cells that safeguard tissue health
Schuster I, Sng X, Lau C, Powell D, Weizman O, Fleming P, Neate G, Voigt V, Sheppard S, Maraskovsky A, Daly S, Koyama M, Hill G, Turner S, O'Sullivan T, Sun J, Andoniou C, Degli-Esposti M. Infection induces tissue-resident memory NK cells that safeguard tissue health. Immunity 2023, 56: 531-546.e6. PMID: 36773607, PMCID: PMC10360410, DOI: 10.1016/j.immuni.2023.01.016.Peer-Reviewed Original ResearchConceptsNK cellsTissue healthAdaptive-like featuresMemory NK cellsNatural killer cellsMurine cytomegalovirus infectionNon-lymphoid tissuesTissue-resident populationsCytomegalovirus infectionInnate cellsInnate lymphocytesKiller cellsAutoimmune diseasesTissue residencyImmune responseAdaptive immunityImmune equilibriumCardinal featuresSalivary glandsAdditional strategiesHealthCellsTissueCD4Response
2021
Neuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2020
Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2
Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, Warren JL, Geng B, Muenker MC, Moore AJ, Vogels CBF, Petrone ME, Ott IM, Lu P, Venkataraman A, Lu-Culligan A, Klein J, Earnest R, Simonov M, Datta R, Handoko R, Naushad N, Sewanan LR, Valdez J, White EB, Lapidus S, Kalinich CC, Jiang X, Kim DJ, Kudo E, Linehan M, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Weizman OE, Wong P, Yang Y, Bermejo S, Odio CD, Omer SB, Dela Cruz CS, Farhadian S, Martinello RA, Iwasaki A, Grubaugh ND, Ko AI. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. New England Journal Of Medicine 2020, 383: 1283-1286. PMID: 32857487, PMCID: PMC7484747, DOI: 10.1056/nejmc2016359.Peer-Reviewed Original ResearchAnalytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets
Vogels CBF, Brito AF, Wyllie AL, Fauver JR, Ott IM, Kalinich CC, Petrone ME, Casanovas-Massana A, Catherine Muenker M, Moore AJ, Klein J, Lu P, Lu-Culligan A, Jiang X, Kim DJ, Kudo E, Mao T, Moriyama M, Oh JE, Park A, Silva J, Song E, Takahashi T, Taura M, Tokuyama M, Venkataraman A, Weizman OE, Wong P, Yang Y, Cheemarla NR, White EB, Lapidus S, Earnest R, Geng B, Vijayakumar P, Odio C, Fournier J, Bermejo S, Farhadian S, Dela Cruz CS, Iwasaki A, Ko AI, Landry ML, Foxman EF, Grubaugh ND. Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets. Nature Microbiology 2020, 5: 1299-1305. PMID: 32651556, PMCID: PMC9241364, DOI: 10.1038/s41564-020-0761-6.Peer-Reviewed Original ResearchConceptsSARS-CoV-2SARS-CoV-2 RTSevere acute respiratory syndrome coronavirusAcute respiratory syndrome coronavirusViral RNA copiesPublic health laboratoriesPublic health interventionsReverse transcription-PCR assaySARS-CoV-2 diagnostic testingDiagnostic assaysTranscription-PCR assaySARS-CoV-2 evolutionQuantitative reverse transcription-PCR assaysRapid diagnostic assaysHealth laboratoriesHealth interventionsDiagnostic testingRNA copiesPrimer-probe setsAssaysLow sensitivityCritical needAnalytical sensitivityIL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
Zhou T, Damsky W, Weizman OE, McGeary MK, Hartmann KP, Rosen CE, Fischer S, Jackson R, Flavell RA, Wang J, Sanmamed MF, Bosenberg MW, Ring AM. IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy. Nature 2020, 583: 609-614. PMID: 32581358, PMCID: PMC7381364, DOI: 10.1038/s41586-020-2422-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesDisease Models, AnimalFemaleHepatocyte Nuclear Factor 1-alphaHistocompatibility Antigens Class IHumansImmunotherapyIntercellular Signaling Peptides and ProteinsInterleukin-18Kaplan-Meier EstimateKiller Cells, NaturalLymphocytes, Tumor-InfiltratingMaleMiceNeoplasmsReceptors, Interleukin-18Stem CellsTumor MicroenvironmentConceptsIL-18IL-18BPT cellsAnti-PD-1 resistant tumorsWild-type IL-18Potent anti-tumor effectsMajor histocompatibility complex class IIL-18 pathwayIL-18 therapyInterleukin-18 pathwayMajor therapeutic barrierStem-like TCF1Anti-tumor immunityTumor-infiltrating lymphocytesNatural killer cellsRecombinant IL-18Histocompatibility complex class IAnti-tumor effectsComplex class IAnti-tumor activityMouse tumor modelsModern immunotherapyPrecursor CD8Effector CD8Exhausted CD8Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding
Weizman O, Krykbaeva I, Bosenburg M, Iwasaki A. Conventional type 2 dendritic cells and natural killer cells mediate control of early metastatic seeding. The Journal Of Immunology 2020, 204: 88.17-88.17. DOI: 10.4049/jimmunol.204.supp.88.17.Peer-Reviewed Original ResearchConventional type 2 dendritic cellsType 2 dendritic cellsImmune cellsMetastatic burdenNK cellsDendritic cellsIntracardiac injectionHost anti-tumor immunityType I IFN-independent mannerAdaptive immune cellsAnti-tumor immunityLocal immune cellsNatural killer cellsSyngeneic mouse modelIFN-independent mannerEarly metastatic seedingMetastatic controlTranscription factor IRF3Killer cellsPrimary tumorMetastatic spreadInnate sensorsMouse modelMetastatic growthMetastatic seeding
2019
Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12
Weizman O, Song E, Adams N, Hildreth A, Riggan L, Krishna C, Aguilar O, Leslie C, Carlyle J, Sun J, O’Sullivan T. Mouse cytomegalovirus-experienced ILC1s acquire a memory response dependent on the viral glycoprotein m12. Nature Immunology 2019, 20: 1004-1011. PMID: 31263280, PMCID: PMC6697419, DOI: 10.1038/s41590-019-0430-1.Peer-Reviewed Original ResearchConceptsInnate lymphoid cellsTissue-resident innate lymphoid cellsType 1 innate lymphoid cellsMouse cytomegalovirusMemory lymphocyte responsesResolution of infectionTissue-resident sentinelsPathogen-derived antigensEarly host protectionLymphocyte responsesBystander activationProinflammatory cytokinesHeterologous infectionsMCMV infectionEffector responsesSecondary challengeHost protectionLymphoid cellsMemory responsesInfectionInitial sitePresent studyPhenotypic changesResponseILC1sCytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells
Adams N, Geary C, Santosa E, Lumaquin D, Le Luduec J, Sottile R, van der Ploeg K, Hsu J, Whitlock B, Jackson B, Weizman O, Huse M, Hsu K, Sun J. Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells. Immunity 2019, 50: 1381-1390.e5. PMID: 31103381, PMCID: PMC6614060, DOI: 10.1016/j.immuni.2019.04.009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytomegalovirusCytomegalovirus InfectionsCytotoxicity, ImmunologicGene Expression RegulationHerpesviridae InfectionsHost-Pathogen InteractionsHumansImmunologic MemoryKiller Cells, NaturalLymphocyte ActivationMiceMice, KnockoutMuromegalovirusNK Cell Lectin-Like Receptor Subfamily AT-Cell Antigen Receptor SpecificityConceptsNatural killer cellsNK cellsKiller cellsNK cell effector functionsMemory NK cellsNK cell poolHuman NK cellsCell effector functionsHuman CMV infectionCMV infectionCytomegalovirus infectionInnate lymphocytesAdaptive immunityAntiviral immunityEffector functionsRelevant antigensPreferential expansionHigh avidityCell avidityAntigen receptorCell poolAvidityAffinity maturationInfectionImmunityCytomegalovirus infection drives avidity selection of natural killer cells
Adams N, Lumaquin D, Santosa E, Whitlock B, Jackson B, Le Luduec J, Sottile R, Weizman O, Huse M, Hsu K, Sun J. Cytomegalovirus infection drives avidity selection of natural killer cells. The Journal Of Immunology 2019, 202: 76.3-76.3. DOI: 10.4049/jimmunol.202.supp.76.3.Peer-Reviewed Original ResearchNK cell poolNK cellsNatural killer cellsKiller cellsImmune responseNK cell effector functionsNK cell populationHuman NK cellsIFN-γ productionCell effector functionsCell poolSecondary immune responseAntiviral immune responseHuman CMV infectionGreater receptor affinityGreater clonal expansionCMV infectionCytomegalovirus infectionInnate lymphocytesAvidity maturationInfectious challengeMCMV infectionReceptor expressionVirus infectionEffector functions
2018
Epigenetic control of innate and adaptive immune memory
Lau C, Adams N, Geary C, Weizman O, Rapp M, Pritykin Y, Leslie C, Sun J. Epigenetic control of innate and adaptive immune memory. Nature Immunology 2018, 19: 963-972. PMID: 30082830, PMCID: PMC6225771, DOI: 10.1038/s41590-018-0176-1.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCD8-Positive T-LymphocytesCells, CulturedChromatinClonal Selection, Antigen-MediatedEpigenesis, GeneticGene Expression ProfilingHerpesviridae InfectionsImmunity, InnateImmunologic MemoryKiller Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutMuromegalovirusSTAT1 Transcription FactorSTAT4 Transcription FactorConceptsMammalian adaptive immune responseNK cellsDistinct epigenetic signaturesChromatin profilingAdaptive immune memoryAdaptive traitsEpigenetic controlTranscriptional statesNatural killer cellsT cell responsesAdaptive immune responsesEpigenetic modificationsEpigenetic signaturesTranscription factorsEpigenetic profilesInnate immune systemAccessibility stateRegulatory programsCanonical CD8Killer cellsImmunological memorySame infectionLymphocyte memoryT cellsImmune responseTranscription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response
Adams N, Lau C, Fan X, Rapp M, Geary C, Weizman O, Diaz-Salazar C, Sun J. Transcription Factor IRF8 Orchestrates the Adaptive Natural Killer Cell Response. Immunity 2018, 48: 1172-1182.e6. PMID: 29858012, PMCID: PMC6233715, DOI: 10.1016/j.immuni.2018.04.018.Peer-Reviewed Original ResearchConceptsNK cellsViral infectionAdaptive natural killer cell responsesVirus-specific NK cellsNatural killer cell responsesNK cell deficiencyNK cell functionNatural killer cellsNK cell proliferationSevere viral infectionsMouse cytomegalovirus (MCMV) infectionIRF8 mutationsTranscription factor STAT4Cytomegalovirus infectionInnate lymphocytesKiller cellsViral exposureCell deficiencyAdaptive immunityAntiviral immunityTranscription factor IRF8Cell responsesBiallelic mutationsViral susceptibilityInfection
2017
Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses
Rapp M, Lau C, Adams N, Weizman O, O'Sullivan T, Geary C, Sun J. Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses. Science Immunology 2017, 2 PMID: 29222089, PMCID: PMC6265048, DOI: 10.1126/sciimmunol.aan3796.Peer-Reviewed Original ResearchConceptsRunx transcription factorsTranscription factorsGene locusNK cellsTranscription factor signal transducerCell cycle programCore-binding factor βHistone mark H3K4me3Epigenetic controlAdaptive natural killer cell responsesChromatin immunoprecipitationEpigenetic modificationsClonal expansionNatural killer cell responsesSignal transducerPromoter regionMemory NK cellsNatural killer cellsNK cell activationTranscription 4Cycle programSpecific ablationInnate lymphocytesKiller cellsFactor βILC1 Confer Early Host Protection at Initial Sites of Viral Infection
Weizman O, Adams N, Schuster I, Krishna C, Pritykin Y, Lau C, Degli-Esposti M, Leslie C, Sun J, O’Sullivan T. ILC1 Confer Early Host Protection at Initial Sites of Viral Infection. Cell 2017, 171: 795-808.e12. PMID: 29056343, PMCID: PMC5687850, DOI: 10.1016/j.cell.2017.09.052.Peer-Reviewed Original ResearchConceptsImmune cellsViral infectionType 1 innate lymphoid cellsInitial antiviral responseInnate lymphoid cellsTissue-resident lymphocytesConventional dendritic cellsInnate immune cellsSite of infectionEarly antiviral immunityEarly host protectionViral burdenDendritic cellsViral loadProinflammatory cytokinesPrimary infectionAntiviral immunityHost protectionLymphoid cellsHost immunityInitial infectionAntiviral responseInfectionSTAT4-dependent mannerInitial site
2016
Epitope-Specific Vaccination Limits Clonal Expansion of Heterologous Naive T Cells during Viral Challenge
Johnson L, Weizman O, Rapp M, Way S, Sun J. Epitope-Specific Vaccination Limits Clonal Expansion of Heterologous Naive T Cells during Viral Challenge. Cell Reports 2016, 17: 636-644. PMID: 27732841, PMCID: PMC5503750, DOI: 10.1016/j.celrep.2016.09.019.Peer-Reviewed Original ResearchConceptsRecall responsesClonal expansionDifferent dendritic cellsInnate lymphocyte responsesRobust recall responsesPrimary immune responseNaive T cellsDifferent activation requirementsHeterotypic antigensMemory CD8Dendritic cellsLymphocyte responsesNaive CD8NK cellsCell primingProtective immunityDistinct anatomical locationsPrior infectionVaccination strategiesViral challengeT cellsImmune responseCell epitopesSecondary epitopesHeterologous antigensAdipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance
O’Sullivan T, Rapp M, Fan X, Weizman O, Bhardwaj P, Adams N, Walzer T, Dannenberg A, Sun J. Adipose-Resident Group 1 Innate Lymphoid Cells Promote Obesity-Associated Insulin Resistance. Immunity 2016, 45: 428-441. PMID: 27496734, PMCID: PMC5004886, DOI: 10.1016/j.immuni.2016.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAdipose TissueAnimalsBasic-Leucine Zipper Transcription FactorsCell DifferentiationCells, CulturedCytokinesHumansImmunity, InnateInflammation MediatorsInsulin ResistanceInterferon-gammaInterleukin-12LymphocytesMacrophagesMiceMice, Inbred C57BLMice, TransgenicObesitySTAT4 Transcription FactorT-Box Domain ProteinsConceptsNatural killerInsulin resistanceInnate lymphoid cell functionLocal proinflammatory cytokine productionObesity-Associated Insulin ResistanceNon-barrier tissuesObesity-related pathologiesProinflammatory cytokine productionImmature NK cellsProinflammatory macrophage polarizationGroup 1 ILCsIL-12 receptorLymphoid cell functionAdipose tissue depotsTranscription factor NFIL3Parabiotic miceNK cellsCytokine productionTissue residencyT-betMacrophage polarizationReporter miceTissue depotsMetabolic diseasesEpithelial barrierAtg5 Is Essential for the Development and Survival of Innate Lymphocytes
O’Sullivan T, Geary C, Weizman O, Geiger T, Rapp M, Dorn G, Overholtzer M, Sun J. Atg5 Is Essential for the Development and Survival of Innate Lymphocytes. Cell Reports 2016, 15: 1910-1919. PMID: 27210760, PMCID: PMC4889506, DOI: 10.1016/j.celrep.2016.04.082.Peer-Reviewed Original ResearchConceptsInnate lymphocytesHomeostatic proliferationMature natural killer (NK) cellsInnate lymphoid cell developmentNatural killer cellsCell-intrinsic apoptosisLymphoreplete miceLymphoid cell developmentLymphocyte numbersKiller cellsMetformin treatmentLymphopenic hostsLymphocyte precursorsGroup 1Induction of autophagyLymphocyte survivalILC developmentInducible ablationLymphocytesLymphocyte developmentSurvivalCell developmentAutophagyATG5Cellular survival mechanism
2013
Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome
Deng Z, Glousker G, Molczan A, Fox A, Lamm N, Dheekollu J, Weizman O, Schertzer M, Wang Z, Vladimirova O, Schug J, Aker M, Londoño-Vallejo A, Kaestner K, Lieberman P, Tzfati Y. Inherited mutations in the helicase RTEL1 cause telomere dysfunction and Hoyeraal–Hreidarsson syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e3408-e3416. PMID: 23959892, PMCID: PMC3767560, DOI: 10.1073/pnas.1300600110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBlotting, WesternCell ProliferationCells, CulturedDNA HelicasesDyskeratosis CongenitaFamily HealthFemaleFetal Growth RetardationGene ExpressionGenomic InstabilityHeLa CellsHumansIn Situ Hybridization, FluorescenceIntellectual DisabilityMaleMiceMicrocephalyMutationPedigreeReverse Transcriptase Polymerase Chain ReactionTelomereTelomere ShorteningTelomeric Repeat Binding Protein 1ConceptsHoyeraal-Hreidarsson syndromeHuman RTEL1Growth defectCell divisionRTEL1 mutationsShelterin proteins TRF1DNA damage responseElongation helicase 1Unlimited cell divisionCell cycle arrestGenome stabilityNatural chromosomesProteins TRF1Telomere protectionNuclear factor 2Helicase RTEL1Damage responseTelomeric repeatsHelicase 1Ectopic expressionTelomere dysfunctionLymphoblastoid cell linesEssential functionsDevelopmental defectsRTEL1