2020
Smooth Muscle Cell Reprogramming in Aortic Aneurysms
Chen PY, Qin L, Li G, Malagon-Lopez J, Wang Z, Bergaya S, Gujja S, Caulk AW, Murtada SI, Zhang X, Zhuang ZW, Rao DA, Wang G, Tobiasova Z, Jiang B, Montgomery RR, Sun L, Sun H, Fisher EA, Gulcher JR, Fernandez-Hernando C, Humphrey JD, Tellides G, Chittenden TW, Simons M. Smooth Muscle Cell Reprogramming in Aortic Aneurysms. Cell Stem Cell 2020, 26: 542-557.e11. PMID: 32243809, PMCID: PMC7182079, DOI: 10.1016/j.stem.2020.02.013.Peer-Reviewed Original ResearchConceptsSmooth muscle cellsAortic aneurysmAneurysm developmentMedial smooth muscle cellsAortic aneurysm developmentContractile smooth muscle cellsGrowth factor βHypercholesterolemic dietSmooth muscleAortic wallMesenchymal stem cellsMuscle cellsAneurysmsMarked increaseFactor βExuberant growthStem cellsHuman diseasesCell massCellsAtherosclerosisHypercholesterolemiaInflammationAortaApoE
2019
Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis
Mensah KA, Chen JW, Schickel JN, Isnardi I, Yamakawa N, Vega-Loza A, Anolik JH, Gatti RA, Gelfand EW, Montgomery RR, Horowitz MC, Craft JE, Meffre E. Impaired ATM activation in B cells is associated with bone resorption in rheumatoid arthritis. Science Translational Medicine 2019, 11 PMID: 31748230, PMCID: PMC7167286, DOI: 10.1126/scitranslmed.aaw4626.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisB cellsHealthy donor controlsGroup of patientsHumanized mouse modelImmature B cellsGene segment usageErosive diseaseRA pathophysiologyBone erosionBone lossBone resorptionHigh prevalenceRANKL productionBone densityMouse modelReceptor activatorBone marrowPatientsDonor controlsCD21Segment usageArthritisElevated frequencyAtaxia telangiectasiaHIPK2 is necessary for type I interferon–mediated antiviral immunity
Cao L, Yang G, Gao S, Jing C, Montgomery RR, Yin Y, Wang P, Fikrig E, You F. HIPK2 is necessary for type I interferon–mediated antiviral immunity. Science Signaling 2019, 12 PMID: 30890658, PMCID: PMC6893850, DOI: 10.1126/scisignal.aau4604.Peer-Reviewed Original ResearchConceptsHomeodomain-interacting protein kinase 2Type I interferonProtein kinase 2I interferonRNA virus infectionAntiviral immunityN-terminal fragmentVesicular stomatitis virus infectionNuclear localizationActive caspasesKinase activityB transcriptionHIPK2 deficiencyKinase 2Virus infectionStomatitis virus infectionAntiviral responseWild-type miceVSV infectionAedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice
Uraki R, Hastings AK, Marin-Lopez A, Sumida T, Takahashi T, Grover JR, Iwasaki A, Hafler DA, Montgomery RR, Fikrig E. Aedes aegypti AgBR1 antibodies modulate early Zika virus infection of mice. Nature Microbiology 2019, 4: 948-955. PMID: 30858571, PMCID: PMC6533137, DOI: 10.1038/s41564-019-0385-x.Peer-Reviewed Original ResearchConceptsZika virus infectionVirus infectionZika virusAegypti salivary proteinsGuillain-Barre syndromeEarly inflammatory responseSkin of micePrevention of mosquitoInflammatory responseAedes aegypti mosquitoesTherapeutic measuresSalivary factorsSalivary proteinsMosquito-borneInfectionMiceSubstantial mortalityRecent epidemicProtein 1Aegypti mosquitoesAntigenic proteinsVirusAntibodiesMosquitoesAntiserum
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
Humanized 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 mice
2016
Mx1 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
Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis
Hwang SH, Jung SH, Lee S, Choi S, Yoo SA, Park JH, Hwang D, Shim SC, Sabbagh L, Kim KJ, Park SH, Cho CS, Kim BS, Leng L, Montgomery RR, Bucala R, Chung YJ, Kim WU. Leukocyte-specific protein 1 regulates T-cell migration in rheumatoid arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e6535-e6543. PMID: 26554018, PMCID: PMC4664344, DOI: 10.1073/pnas.1514152112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalArthritis, RheumatoidCalcium-Binding ProteinsCell MovementCells, CulturedChronic DiseaseExtracellular Signal-Regulated MAP KinasesGene DosageGene Expression ProfilingGenetic Predisposition to DiseaseHumansHypersensitivity, DelayedInflammationMiceMicrofilament ProteinsPhosphorylationReceptors, Antigen, T-CellT-LymphocytesConceptsT cell migrationRheumatoid arthritisT cellsImmune dysfunctionPathogenesis of RAPeripheral T cellsT cell activationT cell receptor activationProtein expression levelsLymph nodesChronic inflammationCytokine responsesInflamed synoviumAutoimmune diseasesLeukocyte-specific protein 1Primary T cellsRA susceptibilityReceptor activationDisease severityMigratory capacityLSP1 geneDiminished expressionTarget tissuesCell motilityProtein 1
2014
Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis
Zhou Y, Peng H, Sun H, Peng X, Tang C, Gan Y, Chen X, Mathur A, Hu B, Slade MD, Montgomery RR, Shaw AC, Homer RJ, White ES, Lee CM, Moore MW, Gulati M, Lee CG, Elias JA, Herzog EL. Chitinase 3–Like 1 Suppresses Injury and Promotes Fibroproliferative Responses in Mammalian Lung Fibrosis. Science Translational Medicine 2014, 6: 240ra76. PMID: 24920662, PMCID: PMC4340473, DOI: 10.1126/scitranslmed.3007096.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisCHI3L1 levelsChitinase 3Lungs of patientsAlternative macrophage activationLevel of apoptosisAcute exacerbationFibroproliferative repairLung transplantationDisease exacerbationInjury phaseAmbulatory patientsEpithelial injuryPulmonary fibrosisIPF populationLung fibrosisMacrophage accumulationCHI3L1 expressionFibrotic phaseDisease progressionProfibrotic roleFibroproliferative responseMacrophage activationMyofibroblast transformationProtective role
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 virusAge-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 ResearchConceptsMetabolic 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
Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis
Reilkoff RA, Peng H, Murray LA, Peng X, Russell T, Montgomery R, Feghali-Bostwick C, Shaw A, Homer RJ, Gulati M, Mathur A, Elias JA, Herzog EL. Semaphorin 7a+ Regulatory T Cells Are Associated with Progressive Idiopathic Pulmonary Fibrosis and Are Implicated in Transforming Growth Factor-β1–induced Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2012, 187: 180-188. PMID: 23220917, PMCID: PMC3570653, DOI: 10.1164/rccm.201206-1109oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisRegulatory T cellsProgressive idiopathic pulmonary fibrosisSEMA 7ATGF-β1Pulmonary fibrosisLung fibrosisT cellsMurine lungIL-10Bone marrow-derived cellsAdoptive transfer approachT-cell mediatorsMarrow-derived cellsTransforming Growth Factor-β1Murine lung fibrosisGrowth factor-β1Lung CD4Adoptive transferIL-17AIL-4Disease progressionSemaphorin 7ACD4Mouse modelSemaphorin 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
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 virusMiceFusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseasesInhibition of Neutrophil Function by Two Tick Salivary Proteins
Guo X, Booth CJ, Paley MA, Wang X, DePonte K, Fikrig E, Narasimhan S, Montgomery RR. Inhibition of Neutrophil Function by Two Tick Salivary Proteins. Infection And Immunity 2009, 77: 2320-2329. PMID: 19332533, PMCID: PMC2687334, DOI: 10.1128/iai.01507-08.Peer-Reviewed Original ResearchConceptsPolymorphonuclear leukocytesPMN functionNumber of PMNPMN integrinsPMN adherenceNeutrophil functionSpirochete burdenTick salivary proteinsTick salivaLyme diseaseTick attachmentSalivary glandsBorrelia burgdorferiTick feedingCausative agentReduced levelsInhibitory proteinSalivaBlood mealAntihemostatic activityInfectionInhibitionSalivary proteinsHematophagous arthropodsTick Ixodes scapularisToll-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
2008
Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain
Wang P, Dai J, Bai F, Kong KF, Wong SJ, Montgomery RR, Madri JA, Fikrig E. Matrix Metalloproteinase 9 Facilitates West Nile Virus Entry into the Brain. Journal Of Virology 2008, 82: 8978-8985. PMID: 18632868, PMCID: PMC2546894, DOI: 10.1128/jvi.00314-08.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinase-9Blood-brain barrierWest Nile virusWNV entryMetalloproteinase-9MMP9 expressionWNV infectionIntact blood-brain barrierBlood-brain barrier permeabilityBrain viral loadWest Nile virus entryEvans blue leakageMosquito-borne encephalitisWest Nile encephalitisLethal WNV challengeWild-type miceCentral nervous systemType IV collagen degradationPeripheral viremiaViral loadLeukocyte infiltrateInflammatory cytokinesLikely multifactorialBarrier permeabilityHost cytokines
2007
Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion
Arjona A, Foellmer HG, Town T, Leng L, McDonald C, Wang T, Wong SJ, Montgomery RR, Fikrig E, Bucala R. Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion. Journal Of Clinical Investigation 2007, 117: 3059-3066. PMID: 17909632, PMCID: PMC1994625, DOI: 10.1172/jci32218.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorMigration inhibitory factorViral neuroinvasionWest Nile virusInvolvement of MIFInhibitory factorProinflammatory cytokine macrophage migration inhibitory factorCytokine macrophage migration inhibitory factorWNV-infected miceBlood-brain barrierLife-threatening encephalitisWild-type miceAcute WNV infectionFlavivirus West Nile virusMIF expressionMIF levelsViral loadWNV encephalitisMIF actionPharmacotherapeutic approachesInflammatory responseWNV infectionCerebrospinal fluidSusceptible individualsInnate immunity