Orr-El Weizman
Research
Publications
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 maturationInfectionImmunity