2022
Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
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
2020
How Inflammation Blunts Innate Immunity in Aging
Goldberg EL, Shaw AC, Montgomery RR. How Inflammation Blunts Innate Immunity in Aging. Interdisciplinary Topics In Gerontology And Geriatrics 2020, 43: 1-17. PMID: 32294641, PMCID: PMC8063508, DOI: 10.1159/000504480.Peer-Reviewed Original ResearchConceptsImmune responseInnate immunityPoor vaccine responsesInnate immune cellsFunctional immune responsesResolution of inflammationInnate immune responseBioactive lipid mediatorsSeverity of infectionImpaired tissue repairInnate immune systemInflammation influencesInflammatory changesLymph nodesVaccine responsesChronic inflammationImmune cellsImmune protectionImmune responsivenessAntigen presentationLipid mediatorsCytokine dynamicsTissue surveillanceImmune systemMolecular dysregulationSingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
2018
SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65
Li P, Jin Y, Qi F, Wu F, Luo S, Cheng Y, Montgomery RR, Qian F. SIRT6 Acts as a Negative Regulator in Dengue Virus-Induced Inflammatory Response by Targeting the DNA Binding Domain of NF-κB p65. Frontiers In Cellular And Infection Microbiology 2018, 8: 113. PMID: 29686974, PMCID: PMC5900784, DOI: 10.3389/fcimb.2018.00113.Peer-Reviewed Original ResearchConceptsToll-like receptor 3Dengue virusInflammatory responseDENV infectionDengue disease severityNF-κB p65Innate immune responseNF-κB activationDomain of p65Overexpression of SIRT6Chemokine productionProinflammatory cytokinesDengue patientsInflammatory cytokinesP65 functionImmune responseLike receptorsDisease severityNegative regulatorReceptor 3Variable severityP65SIRT6CytokinesVirus
2017
Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes
Molony RD, Nguyen JT, Kong Y, Montgomery RR, Shaw AC, Iwasaki A. Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes. Science Signaling 2017, 10 PMID: 29233916, PMCID: PMC6429941, DOI: 10.1126/scisignal.aan2392.Peer-Reviewed Original ResearchConceptsType I IFNsI IFNsI interferonOlder adultsIFN inductionRetinoic acid-inducible gene IAcid-inducible gene IHealthy human donorsType I interferonRespiratory influenzaProinflammatory cytokinesVirus infectionType I IFN genesAdult monocytesAntiviral resistanceTranscription factor IRF8IFN responseHuman donorsMonocytesIncreased proteasomal degradationHuman monocytesYoung adultsIRF8 expressionIAV RNAInfected cellsHumanized mouse model supports development, function, and tissue residency of human natural killer cells
Herndler-Brandstetter D, Shan L, Yao Y, Stecher C, Plajer V, Lietzenmayer M, Strowig T, de Zoete MR, Palm NW, Chen J, Blish CA, Frleta D, Gurer C, Macdonald LE, Murphy AJ, Yancopoulos GD, Montgomery RR, Flavell RA. Humanized mouse model supports development, function, and tissue residency of human natural killer cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e9626-e9634. PMID: 29078283, PMCID: PMC5692533, DOI: 10.1073/pnas.1705301114.Peer-Reviewed Original ResearchConceptsHuman natural killer cellsNatural killer cellsHumanized mouse modelCell subsetsKiller cellsLymphoma xenograftsHuman NKMouse modelHuman antitumor immune responsesHuman NK cell subsetsInnate lymphoid cell subsetsBurkitt's lymphoma xenograftsNK cell subpopulationsNK cell subsetsAntitumor immune responseT cell subsetsHuman NK cellsKiller inhibitory receptorsLymphoid cell subsetsSignal regulatory protein alphaHuman immune systemHuman interleukin-15Regulatory protein alphaNK cellsHumanized miceReduced dynamic range of antiviral innate immune responses in aging
Molony RD, Malawista A, Montgomery RR. Reduced dynamic range of antiviral innate immune responses in aging. Experimental Gerontology 2017, 107: 130-135. PMID: 28822811, PMCID: PMC5815956, DOI: 10.1016/j.exger.2017.08.019.Peer-Reviewed Original ResearchMeSH KeywordsAgedAgingCytokinesDendritic CellsHumansImmunity, InnateInflammasomesMonocytesSignal TransductionConceptsInnate immune responseImmune responseAntiviral innate immune responseKey pattern recognition receptorsAltered cytokine responsePattern recognition receptorsAntiviral interferon responseAge-related changesInflammatory mediatorsCytokine responsesChronic inflammationImmune functionNotable impairmentViral infectionInnate immunityRecognition receptorsInterferon responseProgressive declineViral pathogensAverage life spanResponseWorldwide populationParadoxical stateLife spanInflammationThe natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection
Yao Y, Strauss-Albee DM, Zhou JQ, Malawista A, Garcia MN, Murray KO, Blish CA, Montgomery RR. The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection. PLOS ONE 2017, 12: e0172625. PMID: 28235099, PMCID: PMC5325267, DOI: 10.1371/journal.pone.0172625.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntigens, CDAsymptomatic DiseasesFemaleGene Expression RegulationHumansImmunity, InnateImmunophenotypingInterferon-gammaKiller Cells, NaturalLymphocyte ActivationLymphocyte CountMiddle AgedNatural Cytotoxicity Triggering Receptor 1Natural Cytotoxicity Triggering Receptor 2Natural Cytotoxicity Triggering Receptor 3NK Cell Lectin-Like Receptor Subfamily CNK Cell Lectin-Like Receptor Subfamily KPrimary Cell CultureSeverity of Illness IndexWest Nile FeverWest Nile virusConceptsNK cell subsetsNK cellsWest Nile virusWNV infectionCell subsetsCell responsesSpecific NK cell subsetsNatural killer cell responsesInnate NK cellsSevere neuroinvasive diseaseNK cell responsesNK cell receptorsNile virusHuman WNV infectionsImmune pathogenesisNK repertoirePolyfunctional responsesMore IFNSymptomatic infectionChemokine secretionAsymptomatic infectionNeuroinvasive diseasePrior historyCytolytic activityInfection
2016
Role of Immune Aging in Susceptibility to West Nile Virus
Yao Y, Montgomery RR. Role of Immune Aging in Susceptibility to West Nile Virus. Methods In Molecular Biology 2016, 1435: 235-247. PMID: 27188562, PMCID: PMC4941816, DOI: 10.1007/978-1-4939-3670-0_18.Peer-Reviewed Original ResearchConceptsWest Nile virusImmune dysregulationWNV infectionSevere neuroinvasive diseaseInnate immune cellsΓδ T cellsNile virusProminent risk factorAge-dependent dysregulationAge-related alterationsDendritic cellsNK cellsImmune agingNeuroinvasive diseaseImmune cellsRisk factorsT cellsImmune responseSpecific treatmentTherapeutic interventionsOlder peopleInfectionMass cytometryHost susceptibilityDysregulationMx1 reveals innate pathways to antiviral resistance and lethal influenza disease
Pillai PS, Molony RD, Martinod K, Dong H, Pang IK, Tal MC, Solis AG, Bielecki P, Mohanty S, Trentalange M, Homer RJ, Flavell RA, Wagner DD, Montgomery RR, Shaw AC, Staeheli P, Iwasaki A. Mx1 reveals innate pathways to antiviral resistance and lethal influenza disease. Science 2016, 352: 463-466. PMID: 27102485, PMCID: PMC5465864, DOI: 10.1126/science.aaf3926.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultAgedAged, 80 and overAnimalsBacterial InfectionsCaspase 1CaspasesCaspases, InitiatorFemaleHumansImmunity, InnateInfluenza A virusInfluenza, HumanInterferon-betaMaleMembrane GlycoproteinsMiceMonocytesMyxovirus Resistance ProteinsNeutrophilsOrthomyxoviridae InfectionsRespiratory Tract InfectionsToll-Like Receptor 7Viral LoadYoung AdultConceptsBacterial burdenAntiviral resistanceNeutrophil-dependent tissue damageMyD88-dependent signalingAntiviral interferon productionCaspase-1/11IAV diseaseViral loadInfluenza diseaseOlder humansTissue damageInterferon productionInflammasome responseOlder adultsTLR7Vivo consequencesDiseaseMiceIAVBurdenMx geneHumansMonocytesMortalityInfluenza
2015
Paradoxical changes in innate immunity in aging: recent progress and new directions
Montgomery RR, Shaw AC. Paradoxical changes in innate immunity in aging: recent progress and new directions. Journal Of Leukocyte Biology 2015, 98: 937-943. PMID: 26188078, PMCID: PMC4661037, DOI: 10.1189/jlb.5mr0315-104r.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsB-LymphocytesCytokinesHumansImmunity, InnateSignal TransductionT-LymphocytesConceptsImmune responseInnate immune changesInnate immune responseCytokine levelsInappropriate elevationImmune changesNaïve cell populationT cellsAdaptive immunityViral infectionParadoxical increaseInnate immunityMultiple cell typesParadoxical changesCell populationsActivation stateImmunityCell typesSevere consequencesResponseTissue contextImmunosenescenceVaccinationPopulationInfectionRisk factors for West Nile virus infection and disease in populations and individuals
Montgomery RR, Murray KO. Risk factors for West Nile virus infection and disease in populations and individuals. Expert Review Of Anti-infective Therapy 2015, 13: 317-325. PMID: 25637260, PMCID: PMC4939899, DOI: 10.1586/14787210.2015.1007043.Peer-Reviewed Original ResearchConceptsWest Nile virusWest Nile virus infectionComplex immune interactionsRisk factorsAdvanced ageVirus infectionImmune responseSevere diseaseImmune interactionsClinical casesMosquito-borneCDC reportNile virusNaïve bird populationsInfectionDiseasePositive-strand RNA virusesRNA virusesVirusNew York CityHypertensionImmunosuppressionPopulationYork City
2014
Effect of aging on microRNAs and regulation of pathogen recognition receptors
Olivieri F, Procopio AD, Montgomery RR. Effect of aging on microRNAs and regulation of pathogen recognition receptors. Current Opinion In Immunology 2014, 29: 29-37. PMID: 24769423, PMCID: PMC4119513, DOI: 10.1016/j.coi.2014.03.006.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgingAnimalsHumansImmunity, InnateInflammationMicroRNAsReceptors, ImmunologicConceptsInnate immune recognitionImmune innate responseResolution of inflammationPathogen recognition receptorsTLR signalsUnderstanding of immunosenescenceProinflammatory responseImmune responseNF-κBInnate responseImmune recognitionRecognition receptorsActive investigationImmunosenescenceDownstream effectorsRecent studiesNegative regulatorSimilar regulatory activitiesResponseMiRNAsInflammationMicroRNAsAging-associated miRNAsVaccine
2013
Age-dependent dysregulation of innate immunity
Shaw AC, Goldstein DR, Montgomery RR. Age-dependent dysregulation of innate immunity. Nature Reviews Immunology 2013, 13: 875-887. PMID: 24157572, PMCID: PMC4096436, DOI: 10.1038/nri3547.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgingAnimalsHumansImmunity, CellularImmunity, InnateInflammationMiceReceptors, Pattern RecognitionConceptsMetabolic syndromeIntracellular killingInnate immunityToll-like receptor functionNeutrophil extracellular trap formationBasal cytokine productionInnate immune dysregulationDendritic cell populationsMonocyte-derived DCsChronic viral infectionsMyeloid cells-1Pro-inflammatory milieuChronic inflammatory conditionsInnate immune activationVirus-infected macrophagesExtracellular trap formationAge-dependent dysregulationInnate immune systemPattern recognition receptorsAge-associated alterationsMacrophage colony-stimulating factorGranulocyte/macrophage colony-stimulating factorColony-stimulating factorTLR expressionImmune dysregulation
2012
Innate Immune Function by Toll-like Receptors: Distinct Responses in Newborns and the Elderly
Kollmann TR, Levy O, Montgomery RR, Goriely S. Innate Immune Function by Toll-like Receptors: Distinct Responses in Newborns and the Elderly. Immunity 2012, 37: 771-783. PMID: 23159225, PMCID: PMC3538030, DOI: 10.1016/j.immuni.2012.10.014.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedCytokinesDisease SusceptibilityHumansImmunity, InnateInfant, NewbornToll-Like ReceptorsConceptsInnate immune functionEnd of lifeImmune functionReceptor-mediated immune responsesInnate cytokine responsesToll-like receptorsMonths of lifeInnate immune systemHost-environment interactionsClinical patternCytokine responsesExcessive inflammationImmune developmentParticular infectionImmune responseImmune systemRisk periodOlder adultsSimilar patternDevelopmental patternsResponseInflammationNewbornsInfantsInfection
2011
Innate immune control of West Nile virus infection
Arjona A, Wang P, Montgomery RR, Fikrig E. Innate immune control of West Nile virus infection. Cellular Microbiology 2011, 13: 1648-1658. PMID: 21790942, PMCID: PMC3196381, DOI: 10.1111/j.1462-5822.2011.01649.x.Peer-Reviewed Original ResearchConceptsWest Nile virusWNV infectionAntiviral innate immune mechanismsLong-term neurologic sequelaeWest Nile virus infectionRe-emerging zoonotic pathogenInnate immune controlInnate immune mechanismsLife-threatening meningoencephalitisInnate immune systemNeurologic sequelaeImmune controlInflammatory mediatorsImmune mechanismsMammalian hostsVirus infectionCurrent evidenceViral infectionAntiviral effectorsImmune systemFlaviviridae familyAntiviral mechanismInfectionNile virusJAK-STAT
2010
Dysregulation of human Toll-like receptor function in aging
Shaw AC, Panda A, Joshi SR, Qian F, Allore HG, Montgomery RR. Dysregulation of human Toll-like receptor function in aging. Ageing Research Reviews 2010, 10: 346-353. PMID: 21074638, PMCID: PMC3633557, DOI: 10.1016/j.arr.2010.10.007.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAgingDendritic CellsHumansImmunity, InnateMacrophagesSignal TransductionToll-Like ReceptorsConceptsToll-like receptorsTLR functionImmune systemToll-like receptor functionPattern recognition receptor familyAge-associated dysregulationInnate immune systemGeriatric patientsTLR activationAnimal modelsContext of agingReceptor functionHuman cohortsInfectious diseasesReceptor familyInappropriate persistenceDysregulationRecent studiesOverarching themesAdaptive responseMorbidityImmunosenescencePatientsCohortInnate
2009
Human innate immunosenescence: causes and consequences for immunity in old age
Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC. Human innate immunosenescence: causes and consequences for immunity in old age. Trends In Immunology 2009, 30: 325-333. PMID: 19541535, PMCID: PMC4067971, DOI: 10.1016/j.it.2009.05.004.Peer-Reviewed Original ResearchConceptsInnate immune system initiatesNatural killer T cellsOlder ageAntiviral cytokine productionKiller T cellsInnate immune responseInnate immune systemDendritic cellsNatural killerCytokine productionHuman immunosenescenceT cellsImmune responseAdaptive immunityImmune systemInnate immunityImmunityAgeCellsDiverse cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfection
2008
Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly
Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE, Fikrig E, Montgomery RR. Dysregulation of TLR3 Impairs the Innate Immune Response to West Nile Virus in the Elderly. Journal Of Virology 2008, 82: 7613-7623. PMID: 18508883, PMCID: PMC2493309, DOI: 10.1128/jvi.00618-08.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overCell Adhesion MoleculesCell LineCells, CulturedCytokinesFemaleHumansImmunity, InnateLectins, C-TypeMacrophagesMaleMiddle AgedNorth AmericaProtein BindingReceptors, Cell SurfaceSTAT1 Transcription FactorToll-Like Receptor 3Viral Envelope ProteinsWest Nile FeverWest Nile virusConceptsInnate immune responseToll-like receptor 3Intercellular adhesion molecule 3West Nile virusImmune responseYoung donorsC-type lectin dendritic cell-specific intercellular adhesion molecule 3Dendritic cell-specific intercellular adhesion molecule 3Nile virusBlood-brain barrierWNV envelope proteinSevere neurological diseaseResponsiveness of macrophagesPrimary human macrophagesCytokine levelsOlder donorsWNV infectionNeurological diseasesReceptor 3Human macrophagesOlder individualsElevated levelsMacrophagesMolecule 3Significant differences