2019
Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry
Carvajal-Hausdorf DE, Patsenker J, Stanton KP, Villarroel-Espindola F, Esch A, Montgomery RR, Psyrri A, Kalogeras KT, Kotoula V, Foutzilas G, Schalper KA, Kluger Y, Rimm DL. Multiplexed (18-Plex) Measurement of Signaling Targets and Cytotoxic T Cells in Trastuzumab-Treated Patients using Imaging Mass Cytometry. Clinical Cancer Research 2019, 25: 3054-3062. PMID: 30796036, PMCID: PMC6522272, DOI: 10.1158/1078-0432.ccr-18-2599.Peer-Reviewed Original ResearchConceptsTrastuzumab-treated patientsT cell infiltrationCD8 T cell infiltrationCohort of patientsCytotoxic T cellsMass cytometryCase-control seriesExtracellular domainMechanism of actionTrastuzumab benefitAdjuvant treatmentCD8 cellsRecurrence eventsT cellsAntibody panelImmune systemPatientsMetal-conjugated antibodiesQuantitative immunofluorescenceTrastuzumabImaging Mass CytometryHER2Signaling targetsObjective measurementsCytometry
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingDEAD Box Protein 58FemaleHumansImmunity, InnateInterferonsMaleMonocytesReceptors, ImmunologicSignal TransductionConceptsType 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 cellsReduced 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 spanInflammation
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 contextImmunosenescenceVaccinationPopulationInfection
2014
Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling
Lee N, Shin MS, Kang KS, Yoo SA, Mohanty S, Montgomery RR, Shaw AC, Kang I. Human monocytes have increased IFN-γ-mediated IL-15 production with age alongside altered IFN-γ receptor signaling. Clinical Immunology 2014, 152: 101-110. PMID: 24657713, PMCID: PMC4018768, DOI: 10.1016/j.clim.2014.03.003.Peer-Reviewed Original Research
2013
ELF4 is critical for induction of type I interferon and the host antiviral response
You F, Wang P, Yang L, Yang G, Zhao YO, Qian F, Walker W, Sutton R, Montgomery R, Lin R, Iwasaki A, Fikrig E. ELF4 is critical for induction of type I interferon and the host antiviral response. Nature Immunology 2013, 14: 1237-1246. PMID: 24185615, PMCID: PMC3939855, DOI: 10.1038/ni.2756.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCells, CulturedDNA-Binding ProteinsHEK293 CellsHeLa CellsHost-Pathogen InteractionsHumansImmunoblottingInterferon Regulatory Factor-3Interferon Regulatory Factor-7Interferon-betaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ConfocalProtein BindingReverse Transcriptase Polymerase Chain ReactionRNA InterferenceSignal TransductionSurvival AnalysisTranscription FactorsTranscriptional ActivationWest Nile FeverWest Nile virus
2012
Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus
Qian F, Bolen CR, Jing C, Wang X, Zheng W, Zhao H, Fikrig E, Bruce RD, Kleinstein SH, Montgomery RR. Impaired Toll-Like Receptor 3-Mediated Immune Responses from Macrophages of Patients Chronically Infected with Hepatitis C Virus. MSphere 2012, 20: 146-155. PMID: 23220997, PMCID: PMC3571267, DOI: 10.1128/cvi.00530-12.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleGene ExpressionGenotypeHepacivirusHepatitis C, ChronicHumansInflammationInterferon-betaInterferonsInterleukinsLeukocytes, MononuclearMacrophagesMalePhosphorylationPolymorphism, Single NucleotideSignal TransductionSTAT1 Transcription FactorToll-Like Receptor 3Tumor Necrosis Factor-alphaViral LoadConceptsToll-like receptor 3Peripheral blood mononuclear cellsHepatitis C virusImmune responseHCV patientsC virusExpression of TLR3Clearance of HCVCommon chronic blood-borne infectionElevated innate immune responseImpaired toll-like receptorPrimary macrophagesHCV genotype 1Ongoing inflammatory responseMajority of patientsBlood-borne infectionsBlood mononuclear cellsToll-like receptorsIFN response genesPotential therapeutic approachInnate immune responseMacrophages of patientsElevated baseline expressionTLR3 pathwayViral clearanceSemaphorin 7A Contributes to West Nile Virus Pathogenesis through TGF-β1/Smad6 Signaling
Sultana H, Neelakanta G, Foellmer HG, Montgomery RR, Anderson JF, Koski RA, Medzhitov RM, Fikrig E. Semaphorin 7A Contributes to West Nile Virus Pathogenesis through TGF-β1/Smad6 Signaling. The Journal Of Immunology 2012, 189: 3150-3158. PMID: 22896629, PMCID: PMC3496209, DOI: 10.4049/jimmunol.1201140.Peer-Reviewed Original ResearchConceptsRole of Sema7AWNV infectionSemaphorin 7ATGF-β1Lethal West Nile virus infectionViral pathogenesisBlood-brain barrier permeabilityWest Nile Virus PathogenesisWest Nile virus infectionMurine cortical neuronsPrimary human macrophagesViral burdenWNV pathogenesisCortical neuronsBarrier permeabilityFlaviviral infectionsVirus infectionVirus pathogenesisNervous systemImmune systemPathogenesisInfectionHuman macrophagesSema7AMiceIL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis
Wang P, Bai F, Zenewicz LA, Dai J, Gate D, Cheng G, Yang L, Qian F, Yuan X, Montgomery RR, Flavell RA, Town T, Fikrig E. IL-22 Signaling Contributes to West Nile Encephalitis Pathogenesis. PLOS ONE 2012, 7: e44153. PMID: 22952908, PMCID: PMC3429482, DOI: 10.1371/journal.pone.0044153.Peer-Reviewed Original ResearchConceptsWild-type miceCentral nervous systemIL-22Viral loadNeutrophil migrationType miceWest Nile virus encephalitisSimilar viral loadsLethal WNV infectionIL-22 signalingHost immune responseWNV neuroinvasionVirus encephalitisCXCR2 ligandsLeukocyte infiltrateProinflammatory cytokinesChemokine receptorsImmune responseWNV infectionViral infectionNervous systemSignaling contributesExtracellular pathogensNon-redundant roleWT leukocytes
2011
Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly
Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, Bockenstedt L, Malawista S, Bucala R, Shaw AC, Fikrig E, Montgomery RR. Age‐associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell 2011, 11: 104-110. PMID: 22023165, PMCID: PMC3257374, DOI: 10.1111/j.1474-9726.2011.00759.x.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingExtracellular Signal-Regulated MAP KinasesFemaleHumansInflammationInterleukin-8MaleMiddle AgedMonocytesMultivariate AnalysisNF-kappa BP38 Mitogen-Activated Protein KinasesPhosphorylationProtein TransportRNA, MessengerSignal TransductionToll-Like Receptor 5Tumor Necrosis Factor-alphaConceptsToll-like receptorsIL-8Multivariable mixed-effects modelsOlder individualsElevated IL-8Levels of TLR5Expression of TLR5Production of TNFAge-associated elevationAge-related decreaseDendritic cellsImmune responsivenessElderly donorsInflammatory responseImmune functionNF-κBTLR5Progressive declineMonocytesMixed effects modelsMAPK p38Significant increaseEffects modelAssociated increaseCritical mechanismImpaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus
Qian F, Wang X, Zhang L, Lin A, Zhao H, Fikrig E, Montgomery RR. Impaired Interferon Signaling in Dendritic Cells From Older Donors Infected In Vitro With West Nile Virus. The Journal Of Infectious Diseases 2011, 203: 1415-1424. PMID: 21398396, PMCID: PMC3080893, DOI: 10.1093/infdis/jir048.Peer-Reviewed Original ResearchConceptsDendritic cellsWest Nile virusOlder donorsAntiviral responseToll-like receptor 3Initial antiviral responseLate-phase responseNile virusSignificant age-related differencesSignificant human morbidityType I IFNQuantified cytokinesRNA flavivirusAge-related differencesYoung donorsI IFNReceptor RIGViral infectionReceptor 3Human morbidityOlder populationCritical regulatory pathwaysInterferon SignalingNuclear translocationDefective regulation
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 responseMorbidityImmunosenescencePatientsCohortInnateAnaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks
Sultana H, Neelakanta G, Kantor FS, Malawista SE, Fish D, Montgomery RR, Fikrig E. Anaplasma phagocytophilum induces actin phosphorylation to selectively regulate gene transcription in Ixodes scapularis ticks. Journal Of Experimental Medicine 2010, 207: 1727-1743. PMID: 20660616, PMCID: PMC2916137, DOI: 10.1084/jem.20100276.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnaplasma phagocytophilumAnimalsCell LineCell NucleusEnzyme InhibitorsGastrointestinal TractGene ExpressionGene Expression RegulationGTP-Binding Protein beta SubunitsGTP-Binding Protein gamma SubunitsInsect ProteinsIxodesP21-Activated KinasesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPromoter Regions, GeneticProtein BindingRNA InterferenceRNA Polymerase IISalivary GlandsSalivary Proteins and PeptidesSignal TransductionTATA-Box Binding ProteinTranscription, GeneticConceptsRNA polymerase IIActin phosphorylationTATA box-binding proteinNuclear G-actinPhosphorylation of actinP21-activated kinaseA. phagocytophilumA. phagocytophilum survivalTick cell linesIxodes scapularis ticksPolymerase IIPhosphorylated actinGene crucialGbetagamma subunitsGene transcriptionFilamentous actinAnaplasma phagocytophilumGene expressionBacterial acquisitionScapularis ticksPhosphorylationG-actinIntracellular pathogensMedical importanceActin
2009
IL-10 Signaling Blockade Controls Murine West Nile Virus Infection
Bai F, Town T, Qian F, Wang P, Kamanaka M, Connolly TM, Gate D, Montgomery RR, Flavell RA, Fikrig E. IL-10 Signaling Blockade Controls Murine West Nile Virus Infection. PLOS Pathogens 2009, 5: e1000610. PMID: 19816558, PMCID: PMC2749443, DOI: 10.1371/journal.ppat.1000610.Peer-Reviewed Original ResearchConceptsIL-10 signalingIL-10WNV infectionWest Nile virusIL-10-deficient miceWest Nile virus infectionImportant cellular sourceSignificant human morbidityRNA flavivirusWNV pathogenesisInterleukin-10Antiviral cytokinesEtiologic rolePharmacologic blockadeDeficient miceT cellsVirus infectionPharmacologic meansTherapeutic strategiesViral infectionCellular sourceInfectionHuman morbidityNile virusMiceHuman 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 cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionToll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing
Town T, Bai F, Wang T, Kaplan AT, Qian F, Montgomery RR, Anderson JF, Flavell RA, Fikrig E. Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity 2009, 30: 242-253. PMID: 19200759, PMCID: PMC2707901, DOI: 10.1016/j.immuni.2008.11.012.Peer-Reviewed Original ResearchConceptsToll-like receptor 7West Nile virusReceptor 7WNV infectionImmune cell infiltrationLethal WNV infectionMyeloid differentiation factorIL-23 p19IL-23 responsesIL-12 p40West Nile encephalitisIL-12 p35Infected target cellsHost defense mechanismsRNA flavivirusInnate cytokinesWNV encephalitisInterleukin-12Cell infiltrationImmune cellsTarget organsVariable severityMiceTarget cellsTissue concentrations
2007
ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection
Pedra JH, Sutterwala FS, Sukumaran B, Ogura Y, Qian F, Montgomery RR, Flavell RA, Fikrig E. ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-γ Axis during Anaplasma phagocytophilum Infection. The Journal Of Immunology 2007, 179: 4783-4791. PMID: 17878377, DOI: 10.4049/jimmunol.179.7.4783.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnaplasmaAnaplasmosisAnimalsApoptosis Regulatory ProteinsCalcium-Binding ProteinsCaspase 1Disease SusceptibilityEnzyme ActivationHL-60 CellsHumansInterferon-gammaInterleukin-18Killer Cells, NaturalMiceMice, Inbred C57BLMice, KnockoutPhagocytosisSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryConceptsA. phagocytophilum infectionIFN-gamma productionCaspase-1Phagocytophilum infectionIFN-gammaA. phagocytophilumIFN-gamma levelsNOD-like receptor pathwayIL-18 secretionIFN-gamma-mediated controlCentral adaptor moleculeAnaplasma phagocytophilum infectionVitro restimulationIL-18Peripheral bloodControl animalsReceptor pathwayASC deficiencyInfectionObligate intracellular pathogensIntracellular pathogensAnaplasma phagocytophilumPhagocytophilumAdaptor moleculeCritical role