2020
Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF
Stewart E, Wang X, Chupp GL, Montgomery RR. Profiling cellular heterogeneity in asthma with single cell multiparameter CyTOF. Journal Of Leukocyte Biology 2020, 108: 1555-1564. PMID: 32911570, PMCID: PMC8087109, DOI: 10.1002/jlb.5ma0720-770rr.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAsthmaFemaleHumansLymphocytesMacrophagesMaleMiddle AgedNeutrophilsSingle-Cell AnalysisSputumConceptsAirway immune cellsSource of inflammationChronic inflammatory diseaseInflammatory cell typesStudy of pathogenesisMultiple distinct subtypesHeterogeneity of diseaseBronchial epithelial cellsAirway inflammationCell typesAsthmatic patientsClinical responseEosinophilic infiltrateAnalysis of sputumAsthmatic inflammationFunctional statusClinical managementImmune cellsInflammatory diseasesHealthy controlsInflammatory responseAirway cellsSputumDistinct subtypesInflammation
2019
Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.
Lindow JC, Tsay AJ, Montgomery RR, Reis EAG, Wunder EA, Araújo G, Nery NRR, Mohanty S, Shaw AC, Lee PJ, Reis MG, Ko AI. Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study. American Journal Of Tropical Medicine And Hygiene 2019, 101: 585-589. PMID: 31333152, PMCID: PMC6726964, DOI: 10.4269/ajtmh.19-0160.Peer-Reviewed Original ResearchConceptsSevere leptospirosisActivation markersDisease severityNeutrophil Toll-like receptorToll-like receptor 2Acute severe leptospirosisHospitalized leptospirosis patientsNeutrophil activation markersEarly immune responseToll-like receptorsSevere disease outcomesHigh initial bacterial loadFebrile infectionsOrgan dysfunctionLeptospirosis patientsPeripheral neutrophilsNeutrophil responseHealthy controlsImmune mechanismsDisease outcomeObservational studyImmune responseSevere diseaseReceptor 2Tissue damage
2017
Multiparameter Single Cell Profiling of Airway Inflammatory Cells
Yao Y, Welp T, Liu Q, Niu N, Wang X, Britto CJ, Krishnaswamy S, Chupp G, Montgomery RR. Multiparameter Single Cell Profiling of Airway Inflammatory Cells. Cytometry Part B Clinical Cytometry 2017, 92: 12-20. PMID: 27807928, PMCID: PMC5250532, DOI: 10.1002/cyto.b.21491.Peer-Reviewed Original ResearchConceptsSingle-cell methodsComplex trait diseasesSubgroup of asthmaticsSingle-cell analysisMultiparameter single cell analysisMillions of patientsTranscriptional analysisImmunologic underpinningsInduced sputumAirway diseaseAsthmatic patientsAirway samplesCell subsetsImmune statusFunctional statusClinical severityDistinct biologic mechanismsTreatment successPhysiologic manifestationsBiologic mechanismsCystic fibrosisCellular analysisPatientsCytometry studiesU.S. population
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
2014
Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging
Qian F, Guo X, Wang X, Yuan X, Chen S, Malawista SE, Bockenstedt LK, Allore HG, Montgomery RR. Reduced bioenergetics and toll-like receptor 1 function in human polymorphonuclear leukocytes in aging. Aging 2014, 6: 131-139. PMID: 24595889, PMCID: PMC3969281, DOI: 10.18632/aging.100642.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingEnergy MetabolismFemaleHumansMaleNeutrophilsToll-Like Receptor 1Young AdultConceptsToll-like receptor 1Polymorphonuclear leukocytesOlder adultsChemokine IL-8Loss of CD62LAge-dependent deficienciesPotential therapeutic opportunitiesHuman polymorphonuclear leukocytesTLR1 expressionIL-8PMN functionPMN activationMultiple pathwaysImmune functionYoung donorsP38 MAP kinaseReceptor 1Bacterial infectionsTherapeutic opportunitiesProgressive declineGlucose uptakeReduced expressionAdultsStimulationLeukocytes
2012
IL-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
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 cellsImmunosenescenceVaccinationNeutrophilsMonocytesInfectionInhibition 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 scapularis
2006
Recruitment of Macrophages and Polymorphonuclear Leukocytes in Lyme Carditis
Montgomery RR, Booth CJ, Wang X, Blaho VA, Malawista SE, Brown CR. Recruitment of Macrophages and Polymorphonuclear Leukocytes in Lyme Carditis. Infection And Immunity 2006, 75: 613-620. PMID: 17101663, PMCID: PMC1828503, DOI: 10.1128/iai.00685-06.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBorrelia burgdorferiColony Count, MicrobialCytokinesDisease Models, AnimalDisease SusceptibilityDNA, BacterialHeartHistocytochemistryLyme DiseaseMacrophagesMiceMice, Inbred C3HMice, Inbred C57BLMice, KnockoutMyocarditisMyocardiumNeutrophilsPolymerase Chain ReactionReceptors, CCR2Receptors, ChemokineUrinary BladderConceptsLyme carditisPolymorphonuclear leukocytesC3H micePresence of PMNsB. burgdorferi burdenNeutrophil chemokine receptorOrgan-specific pathogenesisChemokine receptor CCR2B. burgdorferiRecruitment of macrophagesWild-type miceB. burgdorferi infectionAbsence of macrophagesFunction of macrophagesPeak diseaseInfected heartsLyme arthritisSevere arthritisHeart lesionsReceptor CCR2Severe inflammationHistopathologic examinationChemokine receptorsBurgdorferi infectionCarditisHuman Neutrophil Calprotectin Reduces the Susceptibility of Borrelia burgdorferi to Penicillin
Montgomery RR, Schreck K, Wang X, Malawista SE. Human Neutrophil Calprotectin Reduces the Susceptibility of Borrelia burgdorferi to Penicillin. Infection And Immunity 2006, 74: 2468-2472. PMID: 16552081, PMCID: PMC1418918, DOI: 10.1128/iai.74.4.2468-2472.2006.Peer-Reviewed Original ResearchConceptsClearance of spirochetesB. burgdorferiSites of inflammationTherapeutic dosesCalprotectinGrowth of spirochetesLeukocyte componentsNeutrophil calprotectinAntibiotic sensitivitySpirochetal agentLyme diseaseTherapeutic antibioticsBorrelia burgdorferiPenicillin GProtein calprotectinInflammationBurgdorferiSpirochetesDiseaseDoxycyclineDosesClearance
2004
Tick Saliva Reduces Adherence and Area of Human Neutrophils
Montgomery RR, Lusitani D, de Boisfleury Chevance A, Malawista SE. Tick Saliva Reduces Adherence and Area of Human Neutrophils. Infection And Immunity 2004, 72: 2989-2994. PMID: 15102811, PMCID: PMC387908, DOI: 10.1128/iai.72.5.2989-2994.2004.Peer-Reviewed Original Research
2003
Calprotectin, an Abundant Cytosolic Protein from Human Polymorphonuclear Leukocytes, Inhibits the Growth of Borrelia burgdorferi
Lusitani D, Malawista SE, Montgomery RR. Calprotectin, an Abundant Cytosolic Protein from Human Polymorphonuclear Leukocytes, Inhibits the Growth of Borrelia burgdorferi. Infection And Immunity 2003, 71: 4711-4716. PMID: 12874352, PMCID: PMC166021, DOI: 10.1128/iai.71.8.4711-4716.2003.Peer-Reviewed Original ResearchConceptsPolymorphonuclear leukocytesB. burgdorferiGranule-poor cytoplastsBorrelia burgdorferiBlood polymorphonuclear leukocytesHuman blood polymorphonuclear leukocytesNumerous polymorphonuclear leukocytesPotent bacteriostatic agentHuman polymorphonuclear leukocytesU-CytAcute inflammationCalprotectinModulatory roleLyme spirocheteLyme diseaseSpecific antibodiesProtein calprotectinBurgdorferiLeukocytesAbundant cytosolic proteinOxidative mechanismsBacteriostatic agentRegrowth assaysQuantitative microscopicInflammation
2002
Borrelia burgdorferi Are Susceptible to Killing by a Variety of Human Polymorphonuclear Leukocyte Components
Lusitani D, Malawista SE, Montgomery RR. Borrelia burgdorferi Are Susceptible to Killing by a Variety of Human Polymorphonuclear Leukocyte Components. The Journal Of Infectious Diseases 2002, 185: 797-804. PMID: 11920297, DOI: 10.1086/339341.Peer-Reviewed Original ResearchConceptsIntact polymorphonuclear leukocytesPolymorphonuclear leukocytesB. burgdorferiKilling of BorreliaHuman neutrophil peptides 1Neutrophil peptide-1Bactericidal/permeability-increasing proteinIntact human polymorphonuclear leukocytesHuman polymorphonuclear leukocytesPermeability-increasing proteinProteinase 3Peptide-1Leukocyte componentsNitric oxideLL-37Specific antibodiesBorrelia burgdorferiBurgdorferiGranule contentsEfficient killingSpirochetesCritical roleKillingLeukocytes
1996
Microbial killing by human neutrophil cytokineplasts: similar suppressive effects of reversible and irreversible inhibitors of nitric oxide synthase
Malawista S, Montgomery R, van Blaricom G. Microbial killing by human neutrophil cytokineplasts: similar suppressive effects of reversible and irreversible inhibitors of nitric oxide synthase. Journal Of Leukocyte Biology 1996, 60: 753-757. PMID: 8975878, DOI: 10.1002/jlb.60.6.753.Peer-Reviewed Original ResearchConceptsNO synthase inhibitorSynthase inhibitorL-NIOMin of incubationMonomethyl-L-arginineNitric oxide synthaseHuman blood neutrophilsSimilar suppressive effectReactive nitrogen intermediatesL-Arg analoguesIrreversible inhibitorBlood neutrophilsOxide synthaseSuppressive effectKilling capacityL-arginineKilling pathwaysHuman neutrophilsL-ArgD-ArgNeutrophilsNitrogen intermediatesMicrobial killingGranule contentsIntact neutrophils
1992
Evidence for reactive nitrogen intermediates in killing of staphylococci by human neutrophil cytoplasts. A new microbicidal pathway for polymorphonuclear leukocytes.
Malawista SE, Montgomery RR, van Blaricom G. Evidence for reactive nitrogen intermediates in killing of staphylococci by human neutrophil cytoplasts. A new microbicidal pathway for polymorphonuclear leukocytes. Journal Of Clinical Investigation 1992, 90: 631-636. PMID: 1379614, PMCID: PMC443143, DOI: 10.1172/jci115903.Peer-Reviewed Original ResearchConceptsReactive nitrogen intermediatesL-arginineNitric oxide synthase inhibitor NGranule-poor cytoplastsKilling of staphylococciNitrogen intermediatesSynthase inhibitor NEffect of NMMAChronic granulomatous diseaseHuman blood neutrophilsHuman neutrophil cytoplastsBlood neutrophilsGranulomatous diseasePolymorphonuclear leukocytesD-arginineIntact PMNsNeutrophil cytoplastsMicrobicidal pathwaysNMMASusceptible targetsMin of incubationModest decreaseInhibitor NStaphylococciOxidase activity