2024
Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology
Phan H, Tsitsiklis A, Maguire C, Haddad E, Becker P, Kim-Schulze S, Lee B, Chen J, Hoch A, Pickering H, van Zalm P, Altman M, Augustine A, Calfee C, Bosinger S, Cairns C, Eckalbar W, Guan L, Jayavelu N, Kleinstein S, Krammer F, Maecker H, Ozonoff A, Peters B, Rouphael N, Montgomery R, Reed E, Schaenman J, Steen H, Levy O, Diray-Arce J, Langelier C, Erle D, Hendrickson C, Kangelaris K, Nguyen V, Lee D, Chak S, Ghale R, Gonzalez A, Jauregui A, Leroux C, Altamirano L, Rashid A, Willmore A, Woodruff P, Krummel M, Carrillo S, Ward A, Patel R, Wilson M, Dandekar R, Alvarenga B, Rajan J, Schroeder A, Fragiadakis G, Mick E, Guerrero Y, Love C, Maliskova L, Adkisson M, Ehrlich L, Melamed E, Rousseau J, Hurley K, Geltman J, Siles N, Rogers J, Kutzler M, Bernui M, Cusimano G, Connors J, Woloszczuk K, Joyner D, Edwards C, Lin E, Melnyk N, Powell D, Kim J, Goonewardene I, Simmons B, Smith C, Martens M, Croen B, Semenza N, Bell M, Furukawa S, McLin R, Tegos G, Rogowski B, Mege N, Ulring K, Holland S, Rosen L, Lee S, Vaysman T, Fernandez-Sesma A, Simon V, Van Bakel H, Gonzalez-Reiche A, Qi J, Carreño J, Singh G, Raskin A, Tcheou J, Khalil Z, van de Guchte A, Farrugia K, Khan Z, Kelly G, Srivastava K, Eaker L, Bermúdez González M, Mulder L, Beach K, Fatou B, Smolen K, Viode A, van Haren S, Jha M, Kho A, Milliren C, Chang A, McEnaney K, Barton B, Lentucci C, Murphy M, Saluvan M, Shaheen T, Liu S, Syphurs C, Albert M, Hayati A, Bryant R, Abraham J, Salehi-Rad R, Rivera A, Sen S, Elashoff D, Ward D, Presnell S, Kohr B, Arnett A, Boddapati A, Tharp G, Pellegrini K, Johnson B, Panganiban B, Huerta C, Anderson E, Samaha H, Sevransky J, Bristow L, Beagle E, Cowan D, Hamilton S, Hodder T, Esserman D, Brito A, Rothman J, Grubaugh N, Ko A, Hafler D, Shaw A, Gygi J, Pawar S, Konstorum A, Chen E, Cotsapas C, Wang X, Xu L, Dela Cruz C, Iwasaki A, Mohanty S, Nelson A, Zhao Y, Farhadian S, Asashima H, Pulendran B, Nadeau R, Rosenberg-Hasson Y, Leipold M, Sigal N, Rogers A, Fernandez A, Manohar M, Do E, Chang I, Vita R, Westendorf K, Corry D, Kheradmand F, Song L, Nelson E, Baden L, Mendez K, Lasky-Su J, Tong A, Rooks R, Sekaly R, Fourati S, McComsey G, Harris P, Sieg S, Ribeiro S, Overton J, Rahman A, Hutton S, Michelotti G, Wong K, Seyfert-Margolis V, Metcalf J, Agudelo Higuita N, Sinko L, Booth J, Messer W, Hough C, Siegel S, Sullivan P, Lu Z, Kraft M, Bime C, Mosier J, Erickson H, Schunk R, Kimura H, Conway M, Atkinson M, Brakenridge S, Ungaro R, Manning B, Oberhaus J, Guirgis F, Borresen B, Anderson M. Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Science Translational Medicine 2024, 16: eadj5154. PMID: 38630846, DOI: 10.1126/scitranslmed.adj5154.Peer-Reviewed Original ResearchConceptsPro-inflammatory genesViral clearanceUpper airwayImmune signaling pathwaysInduction of pro-inflammatory genesBiomarkers of disease severityDelayed viral clearanceImpaired viral clearanceSevere coronavirus disease 2019B cell populationsAge-dependent up-regulationExpression of pro-inflammatory genesHost immune responseSignaling pathwayType I interferon gene expressionCOVID-19 immunopathologyInnate immune signaling pathwaysSerum chemokinesAge-dependent impairmentNaive TMulticenter cohortNasal transcriptomeAcute respiratory syndrome coronavirus 2Monocyte populationsSerum protein profiles
2023
Platelet response to influenza vaccination reflects effects of aging
Konstorum A, Mohanty S, Zhao Y, Melillo A, Vander Wyk B, Nelson A, Tsang S, Blevins T, Belshe R, Chawla D, Rondina M, Gill T, Montgomery R, Allore H, Kleinstein S, Shaw A. Platelet response to influenza vaccination reflects effects of aging. Aging Cell 2023, 22: e13749. PMID: 36656789, PMCID: PMC9924941, DOI: 10.1111/acel.13749.Peer-Reviewed Original ResearchConceptsCommunity-dwelling older adultsPlatelet activationOlder adultsInfluenza vaccinationAge-associated chronic inflammationInfluence platelet functionRNA expressionPro-inflammatory diseasesAge-associated increasePlatelet activation pathwaysAge-associated differencesActivation pathwayPlatelet transcriptomeGeriatric conditionsChronic inflammationImmune responsePlatelet functionPlatelet responseSNF residentsVaccinationActivation responseYoung individualsProtein levelsAdultsYounger participants
2020
Single 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
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 damageTranscriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults
Park H, Shin MS, Kim M, Bilsborrow JB, Mohanty S, Montgomery RR, Shaw AC, You S, Kang I. Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults. Aging Cell 2019, 18: e12960. PMID: 31044512, PMCID: PMC6612637, DOI: 10.1111/acel.12960.Peer-Reviewed Original ResearchConceptsPeripheral blood cellsPeripheral blood mononuclear cellsEffector memory CD8Influenza vaccine responsesEM CD8T cellsIL-7RαMemory CD8Vaccine responsesBlood cellsOlder adultsIL-7 receptor alphaSignature genesBlood mononuclear cellsHuman peripheral whole bloodAge-associated expansionPeripheral whole bloodGene expression profilesAge-associated changesMeta-analysis studyGlobal transcriptomic profilesMononuclear cellsCD8Receptor alphaExpression profilesDissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry
Shin MS, Yim K, Moon K, Park HJ, Mohanty S, Kim JW, Montgomery RR, Shaw AC, Krishnaswamy S, Kang I. Dissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry. Clinical Immunology 2019, 200: 24-30. PMID: 30659916, PMCID: PMC6443094, DOI: 10.1016/j.clim.2019.01.005.Peer-Reviewed Original Research
2018
Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia
Abdelrasoul GN, MacKay S, Salim S, Ismond K, Tamura M, Khalifa C, Mannan E, Lin D, Mandal T, Montgomery R, Wishart D, Chen J, Khadaroo R. Non-invasive Point-of-Care Device To Diagnose Acute Mesenteric Ischemia. ACS Sensors 2018, 3: 2296-2302. PMID: 30335977, DOI: 10.1021/acssensors.8b00558.Peer-Reviewed Original ResearchConceptsGold nanoparticlesBiosensor devicesNon-faradic impedance spectroscopyElectrochemical biosensor deviceNon-invasive pointElectrochemical biosensorDetection antibodyCapture antibodyCare devicesImmediate bedside diagnosisElectrode surfacePhotolithographic techniquesDetection signalSandwich mannerImpedance spectroscopySilicon dioxideBedside translationImpedance signalDevicesTarget proteinsI-FABP concentrationsFatty acid binding proteinNanoparticlesBiosensorSpectroscopy
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
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesAssociation between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis
Das R, Loughran K, Murchison C, Qian F, Leng L, Song Y, Montgomery RR, Loeb M, Bucala R. Association between high expression macrophage migration inhibitory factor (MIF) alleles and West Nile virus encephalitis. Cytokine 2015, 78: 51-54. PMID: 26638028, PMCID: PMC4696904, DOI: 10.1016/j.cyto.2015.11.021.Peer-Reviewed Original ResearchConceptsMacrophage migration inhibitory factorWNV encephalitisWest Nile virusHigh-expression MIF allelesWest Nile virus encephalitisNeuroinvasive WNV diseaseCase-control studyMigration inhibitory factorNorth American patientsMIF locusWNV neuropathogenesisVirus encephalitisViral neuroinvasionInnate cytokinesMIF allelesAmerican patientsTherapeutic targetAnimal modelsWNV diseaseEncephalitisInhibitory factorFunctional polymorphismsPatientsNile virusImportant determinant
2014
Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cellsReduced 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 expressionAdultsStimulationLeukocytesImmune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility
2013
Cytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis
Reis EA, Hagan JE, Ribeiro GS, Teixeira-Carvalho A, Martins-Filho OA, Montgomery RR, Shaw AC, Ko AI, Reis MG. Cytokine Response Signatures in Disease Progression and Development of Severe Clinical Outcomes for Leptospirosis. PLOS Neglected Tropical Diseases 2013, 7: e2457. PMID: 24069500, PMCID: PMC3777885, DOI: 10.1371/journal.pntd.0002457.Peer-Reviewed Original ResearchConceptsSevere pulmonary hemorrhage syndromeIL-10IL-6Mild diseaseClinical outcomesIL-8Disease progressionSevere diseaseSerum cytokine responseDays of symptomsHospital-based surveillanceAnti-inflammatory cytokinesIL-6 levelsCase-control study designPulmonary hemorrhage syndromeSevere clinical outcomesMultiplex bead array assayNon-fatal casesLife-threatening outcomesBead array assayImmunopathogenic roleCytokine profileCytokine stormIL-17ANonfatal outcomesIdentification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis
Qian F, Chung L, Zheng W, Bruno V, Alexander RP, Wang Z, Wang X, Kurscheid S, Zhao H, Fikrig E, Gerstein M, Snyder M, Montgomery RR. Identification of Genes Critical for Resistance to Infection by West Nile Virus Using RNA-Seq Analysis. Viruses 2013, 5: 1664-1681. PMID: 23881275, PMCID: PMC3738954, DOI: 10.3390/v5071664.Peer-Reviewed Original ResearchConceptsCommon gene pathwaysNovel cellular responsesDifferential gene expressionRNA-seq analysisWest Nile virusGene expression analysisPrimary human macrophagesGene isoformsHigh-throughput methodRNA-seqGene pathwaysExpression analysisGenes CriticalKnock-downGene expressionCellular responsesGene changesResistant individualsBiological settingsHuman macrophagesGenesCritical roleAvailable treatmentsHealthy donorsViral infectionAn altered relationship of influenza vaccine-specific IgG responses with T cell immunity occurs with aging in humans
Kang KS, Lee N, Shin MS, Kim SD, Yu Y, Mohanty S, Belshe RB, Montgomery RR, Shaw AC, Kang I. An altered relationship of influenza vaccine-specific IgG responses with T cell immunity occurs with aging in humans. Clinical Immunology 2013, 147: 79-88. PMID: 23578549, PMCID: PMC3634098, DOI: 10.1016/j.clim.2013.02.022.Peer-Reviewed Original ResearchConceptsT cell immunityMemory T cellsIgG responsesHI antibody titersT cellsAntibody titersEffector memoryCell immunityHemagglutinin inhibition antibody titersDistinct T cell subsetsCytokine-producing capacityInactivated influenza vaccineCentral memory cellsT cell subsetsSpecific IgG responseSerum IgG responsesPotent survivalIL-17Influenza vaccineSignificant morbidityCell subsetsElderly peopleProliferative capacityTitersAltered relationship
2011
Impaired 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
Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC. Age-Associated Decrease in TLR Function in Primary Human Dendritic Cells Predicts Influenza Vaccine Response. The Journal Of Immunology 2010, 184: 2518-2527. PMID: 20100933, PMCID: PMC3867271, DOI: 10.4049/jimmunol.0901022.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntibodies, ViralCytokinesDendritic CellsFemaleFlow CytometryHumansInfluenza A Virus, H1N1 SubtypeInfluenza VaccinesInterleukin-12 Subunit p40Interleukin-6Linear ModelsMaleMiddle AgedReverse Transcriptase Polymerase Chain ReactionToll-Like ReceptorsTumor Necrosis Factor-alphaYoung AdultConceptsPrimary human dendritic cellsDendritic cellsHuman dendritic cellsMyeloid DCsPlasmacytoid DCsCytokine productionTLR functionTNF-alphaIntracellular cytokine productionPoor Ab responsesInfluenza vaccine responsesMyeloid dendritic cellsPlasmacytoid dendritic cellsYoung individualsIntracellular cytokine stainingIL-12 productionIFN-alpha productionTLR ligand stimulationTLR gene expressionInnate immune responseAge-Associated DecreaseTLR8 engagementInfluenza immunizationAge-associated effectsCytokine staining