2024
UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original ResearchConceptsRIG-I-like receptorsRIG-I-like receptor signalingCytosolic RIG-I-like receptorsAntiviral immunityPlasma membrane tetheringRNA virus infectionGlucose transportInnate antiviral immunityCytoplasmic RIG-I-like receptorsGolgi matrixGLUT4 translocationRLR signalingViral RNACell surfaceGLUT4GLUT4 expressionGlucose uptakeInterferon responseRNAGlycolytic reprogrammingVirus infectionHuman inflammatory myopathiesGolgiSignalUbiquitinHigh burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children
Watkins T, Green A, Amat J, Cheemarla N, Hänsel K, Lozano R, Dudgeon S, Germain G, Landry M, Schulz W, Foxman E. High burden of viruses and bacterial pathobionts drives heightened nasal innate immunity in children. Journal Of Experimental Medicine 2024, 221: e20230911. PMID: 38949638, PMCID: PMC11215523, DOI: 10.1084/jem.20230911.Peer-Reviewed Original ResearchConceptsBacterial pathobiontsRespiratory virusesBurden of virusesSARS-CoV-2Innate immune activationSARS-CoV-2 viral loadDynamic host-pathogen interactionsInnate immune responseViral coinfectionCytokine profileViral loadNasal virusImmune activationProinflammatory responseIL-1BNasopharyngeal samplesHost-pathogen interactionsImmune responseInterferon responsePathobiontsInnate immunityPaired samplesCXCL10Healthy 1-year-oldVirusAuthor Correction: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Everson R, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson B, Cloughesy T, Liau L, Prins R. Author Correction: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. Nature Communications 2024, 15: 4800. PMID: 38839763, PMCID: PMC11153605, DOI: 10.1038/s41467-024-48995-7.Peer-Reviewed Original ResearchTLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Everson R, Hugo W, Sun L, Antonios J, Lee A, Ding L, Bu M, Khattab S, Chavez C, Billingslea-Yoon E, Salazar A, Ellingson B, Cloughesy T, Liau L, Prins R. TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial. Nature Communications 2024, 15: 3882. PMID: 38719809, PMCID: PMC11078958, DOI: 10.1038/s41467-024-48073-y.Peer-Reviewed Original ResearchConceptsAutologous tumor lysate-pulsed dendritic cellCD8+ T cellsT cellsPoly-ICLCTLR agonistsMalignant gliomasTumor lysate-pulsed dendritic cellsRandomized phase II trialCD4+ T cellsRandomized phase II clinical trialInterferon responsePhase II clinical trialPoly-ICLC treatmentDendritic cell vaccinesPD-1 expressionPhase II trialInterferon responsive gene expressionSystemic immune responsesImmune cell activationII clinical trialsInduction of interferon-inducible genesDelay disease progressionInterferon gene expressionInterferon-inducible genesPD-1Macrophages restrain pathological interferon responses during viral respiratory infection
Rodriguez-Morales P, Hoagland D, Mann A, Yu S, Lai A, Baez Vazquez A, Medzhitov R, Franklin R. Macrophages restrain pathological interferon responses during viral respiratory infection. The Journal Of Immunology 2024, 212: 0536_5144-0536_5144. DOI: 10.4049/jimmunol.212.supp.0536.5144.Peer-Reviewed Original ResearchIFN-I productionOncostatin MBlockade of IFN-I signalingViral stimuliEpithelial cellsIFN-IOSM-deficient miceViral respiratory infectionsTriggered by infectionInflammation-induced pathologyLung epithelial cellsIFN-I responseIFN-I signalingRegulation of inflammationType I interferonPoly(I:CAcute blockadeCytokine oncostatin MRespiratory infectionsUncontrolled inflammationInflammatory responseI interferonInterferon responseRespiratory tractMiceTargeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer
Murayama T, Nakayama J, Jiang X, Miyata K, Morris A, Cai K, Prasad R, Ma X, Efimov A, Belani N, Gerstein E, Tan Y, Zhou Y, Kim W, Maruyama R, Campbell K, Chen L, Yang Y, Balachandran S, Canadas I. Targeting DHX9 triggers tumor-intrinsic interferon response and replication stress in Small Cell Lung Cancer. Cancer Discovery 2024, 14: 468-491. PMID: 38189443, PMCID: PMC10905673, DOI: 10.1158/2159-8290.cd-23-0486.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerDExD/H-box helicase 9Cell lung cancerCold tumorsLung cancerResponse to immune-checkpoint blockadeInnate immunityEnhance immunotherapy efficacyImmune-checkpoint blockadeImmunogenic tumor microenvironmentImmunologically cold tumorsNucleic acid-sensing pathwaysActivate innate immunityAntitumor immunityImmunotherapy efficacyReplication stressTumor microenvironmentTumor growthViral mimicryTumorImmune responseCancer cellsInterferon responseCytoplasmic dsRNACancer
2023
Viral Interference During Influenza A–SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir
Cheemarla N, Watkins T, Mihaylova V, Foxman E. Viral Interference During Influenza A–SARS-CoV-2 Coinfection of the Human Airway Epithelium and Reversal by Oseltamivir. The Journal Of Infectious Diseases 2023, 229: 1430-1434. PMID: 37722683, PMCID: PMC11095529, DOI: 10.1093/infdis/jiad402.Peer-Reviewed Original ResearchSARS-CoV-2 replicationSARS-CoV-2IAV replicationHuman airway epithelial culturesHuman airway epitheliumAirway epithelial culturesHost antiviral responseRobust interferon responseInfluenza infectionRespiratory virusesAirway epitheliumViral infectionAntiviral responseViral interferenceCoinfecting virusSimultaneous infectionHost cell defenseInterferon responseCoinfectionInfectionEpithelial culturesOseltamivirInfluenzaVirusCell defenseRIG-I recognizes metabolite-capped RNAs as signaling ligands
Schweibenz B, Solotchi M, Hanpude P, Devarkar S, Patel S. RIG-I recognizes metabolite-capped RNAs as signaling ligands. Nucleic Acids Research 2023, 51: 8102-8114. PMID: 37326006, PMCID: PMC10450190, DOI: 10.1093/nar/gkad518.Peer-Reviewed Original ResearchConceptsRIG-IRNA endsRIG-I signaling pathwayIn vitro transcriptionRIG-I signalingDouble-stranded RNAInnate antiviral immune responseInterferon responseReceptor RIG-ICellular signaling assaysCapped RNACellular rolesPathogenic RNAsViral genomeEndogenous mRNAReplication intermediatesM7GSignaling ligandsImmune responseInnate immune receptor RIG-ISignaling pathwayRNASignaling assaysATPase activityAntiviral immune responseNasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study
Cheemarla N, Hanron A, Fauver J, Bishai J, Watkins T, Brito A, Zhao D, Alpert T, Vogels C, Ko A, Schulz W, Landry M, Grubaugh N, van Dijk D, Foxman E. Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study. The Lancet Microbe 2023, 4: e38-e46. PMID: 36586415, PMCID: PMC9835789, DOI: 10.1016/s2666-5247(22)00296-8.Peer-Reviewed Original ResearchConceptsRespiratory virus panelPg/mLCXCL10 concentrationsSARS-CoV-2Bacterial pathobiontsRespiratory virusesSARS-CoV-2 negative samplesViral respiratory infectionsSARS-CoV-2 positive samplesClinical virology laboratoryHealth care systemVirus-positive samplesQuantitative RT-PCRInfluenza C virusSymptomatic patientsRespiratory infectionsSeasonal coronavirusesNasopharyngeal swabsVirus panelC virusCommon virusesCXCL10Host responseInterferon responseVirology laboratory
2022
circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment
Piras R, Ko E, Barrett C, De Simone M, Lin X, Broz M, Tessaro F, Castillo-Martin M, Cordon-Cardo C, Goodridge H, Di Vizio D, Batish M, Lawrenson K, Chen Y, Chan K, Guarnerio J. circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment. Nature Communications 2022, 13: 7243. PMID: 36433954, PMCID: PMC9700836, DOI: 10.1038/s41467-022-34872-8.Peer-Reviewed Original ResearchConceptsNon-coding RNA speciesExonic circular RNAsViral RNA sensorsRNA speciesInterferon-related genesSpecific circRNAsCircular RNAsSarcoma cellsCircRNAsRNA sensorsCancer progressionFunctional contributionInterferon responseSoft tissue sarcoma cellsImmune cell recruitmentPro-tumorigenic microenvironmentCellsTumor growthSarcoma growthTumor cellsPro-inflammatory elementsCell recruitmentActivationPro-inflammatory factorsMicroenvironmentThe matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
Ryu S, Sidorov S, Ravussin E, Artyomov M, Iwasaki A, Wang A, Dixit VD. The matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging. Immunity 2022, 55: 1609-1626.e7. PMID: 35963236, PMCID: PMC9474643, DOI: 10.1016/j.immuni.2022.07.007.Peer-Reviewed Original ResearchConceptsToll-like receptor 4ISG inductionMatricellular proteinPro-inflammatory phenotypeAnti-inflammatory macrophagesInterferon-stimulated gene expressionAdipocyte-specific deletionInhibition of glycolysisImmunometabolic adaptationsMyD88 pathwayReceptor 4Chronic diseasesFunctional declineCaloric restrictionInterferon responseHealth spanMacrophagesInflammationMitochondrial respirationSPARCInductionGene expressionAdipokinesObesityIFN
2021
KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements
Zhang SM, Cai WL, Liu X, Thakral D, Luo J, Chan LH, McGeary MK, Song E, Blenman KRM, Micevic G, Jessel S, Zhang Y, Yin M, Booth CJ, Jilaveanu LB, Damsky W, Sznol M, Kluger HM, Iwasaki A, Bosenberg MW, Yan Q. KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements. Nature 2021, 598: 682-687. PMID: 34671158, PMCID: PMC8555464, DOI: 10.1038/s41586-021-03994-2.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorDNA-Binding ProteinsEpigenesis, GeneticGene SilencingHeterochromatinHistone-Lysine N-MethyltransferaseHumansInterferon Type IJumonji Domain-Containing Histone DemethylasesMaleMelanomaMiceMice, Inbred C57BLMice, KnockoutNuclear ProteinsRepressor ProteinsRetroelementsTumor EscapeConceptsImmune checkpoint blockadeImmune evasionCheckpoint blockadeImmune responseAnti-tumor immune responseRobust adaptive immune responseTumor immune evasionAnti-tumor immunityAdaptive immune responsesType I interferon responseDNA-sensing pathwayMouse melanoma modelImmunotherapy resistanceMost patientsCurrent immunotherapiesTumor immunogenicityImmune memoryMelanoma modelCytosolic RNA sensingRole of KDM5BConsiderable efficacyInterferon responseImmunotherapyEpigenetic therapyBlockadeTargeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity
Hu H, Khodadadi-Jamayran A, Dolgalev I, Cho H, Badri S, Chiriboga LA, Zeck B, De Rodas Gregorio M, Dowling CM, Labbe K, Deng J, Chen T, Zhang H, Zappile P, Chen Z, Ueberheide B, Karatza A, Han H, Ranieri M, Tang S, Jour G, Osman I, Sucker A, Schadendorf D, Tsirigos A, Schalper KA, Velcheti V, Huang HY, Jin Y, Ji H, Poirier JT, Li F, Wong KK. Targeting the Atf7ip–Setdb1 Complex Augments Antitumor Immunity by Boosting Tumor Immunogenicity. Cancer Immunology Research 2021, 9: 1298-1315. PMID: 34462284, PMCID: PMC9414288, DOI: 10.1158/2326-6066.cir-21-0543.Peer-Reviewed Original ResearchConceptsHistone lysine methyltransferase 1Common adaptive mechanismSuppressor screenChromatin modifiersIntron retentionSET domainEpigenetic regulatorsEpigenetic modificationsEpigenetic modifiersType I interferon responseMethyltransferase 1I interferon responseHuman cancersTranscription factor 7Immune invasionInterferon responseAdaptive mechanismsFactor 7GenesCritical roleExpressionImmune evasionRejection of cellsAntigen processingAntigen expressionAltered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease
Madany E, Lee J, Halprin C, Seo J, Baca N, Majlessipour F, Hendrickson JE, Pepkowitz SH, Hayes C, Klapper E, Gibb DR. Altered type 1 interferon responses in alloimmunized and nonalloimmunized patients with sickle cell disease. EJHaem 2021, 2: 700-710. PMID: 35128535, PMCID: PMC8813163, DOI: 10.1002/jha2.270.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsSickle cell diseaseCell diseaseRace-matched healthy controlsType 1 interferon responseFrequency of alloimmunizationNon-alloimmunized patientsBlood mononuclear cellsType 1 interferonExpression of ISGsGene scoreNonalloimmunized patientsRBC alloimmunizationPlasma cytokinesSCD patientsMononuclear cellsHealthy controlsHigh prevalenceBlood leukocytesAlloimmunizationViral immunityPatientsIFNISG expressionInterferon responseSingle-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma
Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Respiratory Research 2021, 22: 122. PMID: 33902571, PMCID: PMC8074196, DOI: 10.1186/s12931-021-01709-9.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsSevere asthmaEffector T cellsBlood mononuclear cellsT cellsHealthy controlsPoly IDendritic cellsMononuclear cellsUnstimulated peripheral blood mononuclear cellsInterferon responseTLR3 agonist poly IImpaired interferon responseMain cell subsetsNatural killer cellsPro-inflammatory profilePro-inflammatory pathwaysC stimulationCyTOF profilingHigh CD8Cell typesEffector cellsKiller cellsCell subsetsMain cell typesFunctional landscape of SARS-CoV-2 cellular restriction
Martin-Sancho L, Lewinski MK, Pache L, Stoneham CA, Yin X, Becker ME, Pratt D, Churas C, Rosenthal SB, Liu S, Weston S, De Jesus PD, O'Neill AM, Gounder AP, Nguyen C, Pu Y, Curry HM, Oom AL, Miorin L, Rodriguez-Frandsen A, Zheng F, Wu C, Xiong Y, Urbanowski M, Shaw ML, Chang MW, Benner C, Hope TJ, Frieman MB, García-Sastre A, Ideker T, Hultquist JF, Guatelli J, Chanda SK. Functional landscape of SARS-CoV-2 cellular restriction. Molecular Cell 2021, 81: 2656-2668.e8. PMID: 33930332, PMCID: PMC8043580, DOI: 10.1016/j.molcel.2021.04.008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDBinding SitesCell Line, TumorChlorocebus aethiopsEndoplasmic ReticulumGene Expression RegulationGolgi ApparatusGPI-Linked ProteinsHEK293 CellsHost-Pathogen InteractionsHumansImmunity, InnateInterferon Regulatory FactorsInterferon Type IMolecular Docking SimulationProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsSARS-CoV-2Signal TransductionVero CellsViral ProteinsVirus InternalizationVirus ReleaseVirus ReplicationConceptsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-1 infectionSyndrome coronavirus 2 infectionSevere coronavirus disease 2019SARS-CoV-2 infectionCoronavirus 2 infectionInnate immune controlCoronavirus disease 2019Potential therapeutic strategySARS-CoV-2BST2/tetherinImmune controlSet of ISGsDisease 2019Host determinantsTherapeutic strategiesViral infectionAntiviral ISGsDisease severityViral replicationInterferon responseViral entryIFN controlInfectionMulti-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses
Zheng H, Rao A, Dermadi D, Toh J, Jones L, Donato M, Liu Y, Su Y, Dai C, Kornilov S, Karagiannis M, Marantos T, Hasin-Brumshtein Y, He Y, Giamarellos-Bourboulis E, Heath J, Khatri P. Multi-cohort analysis of host immune response identifies conserved protective and detrimental modules associated with severity across viruses. Immunity 2021, 54: 753-768.e5. PMID: 33765435, PMCID: PMC7988739, DOI: 10.1016/j.immuni.2021.03.002.Peer-Reviewed Original ResearchConceptsAnalysis of host immune responsesMyeloid-derived suppressor cellsViral infectionSevere outcomesAssociated with disease severityHost responsePatients aged 0Severe viral infectionsHost-directed therapiesBlood transcriptome profilesHost immune responseSingle-cell RNA sequencing profilesSuppressor cellsImmune cellsGlobal pandemic preparednessImmune responseBacterial infectionsRNA sequencing profilesInterferon responseDisease severitySequence profilesPatientsSARS-CoV-2Gene modulesAged 0Neuroinvasion 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 ACE2InfectionTranslational regulation of viral RNA in the type I interferon response
Hsu J, Laurent-Rolle M, Cresswell P. Translational regulation of viral RNA in the type I interferon response. Current Research In Virological Science 2021, 2: 100012. DOI: 10.1016/j.crviro.2021.100012.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsInterferon-stimulated genesViral infectionViral replicationIFN-I responsesType I interferon responseAntigen-independent mannerInnate immune responseVariety of mechanismsI interferon responseImmune responseVirus life cycleInfectious organismsInterferon responseHost factorsInfectionFirst lineViral RNAViral proteinsType IViral translationCommon cellular responseMolecular mechanismsInhibitionCellular responsesTranslation inhibition
2020
An in vivo atlas of host–pathogen transcriptomes during Streptococcus pneumoniae colonization and disease
D’Mello A, Riegler AN, Martínez E, Beno SM, Ricketts TD, Foxman EF, Orihuela CJ, Tettelin H. An in vivo atlas of host–pathogen transcriptomes during Streptococcus pneumoniae colonization and disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 33507-33518. PMID: 33318198, PMCID: PMC7777036, DOI: 10.1073/pnas.2010428117.Peer-Reviewed Original ResearchConceptsStreptococcus pneumoniae colonizationHost gene expression profilesHost defense pathwaysOrgan damagePneumoniae colonizationProinflammatory responseInvasive diseaseAnatomical sitesTherapeutic targetInterferon responseDisease statesDiseaseGene expression profilesLungOrgan-specific mannerVivoPneumoniaPathogenesisKidneyBloodResponse
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