2023
Early cellular and molecular signatures correlate with severity of West Nile virus infection
Lee H, Zhao Y, Fleming I, Mehta S, Wang X, Vander Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.Peer-Reviewed Original ResearchWest Nile virusEffective anti-viral responseInnate immune cell typesWest Nile virus infectionPro-inflammatory markersAcute time pointsImmune cell typesAnti-viral responseMolecular signaturesHost cellular activitiesAcute infectionAsymptomatic donorsPeripheral bloodSevere infectionsVirus infectionImmune responseSevere casesCell activityIll individualsSerum proteomicsInfectionInfection severityHigh expressionTime pointsNile virusProteome Analysis for Inflammation Related to Acute and Convalescent Infection
Sigdel T, Sur S, Boada P, McDermott S, Arlehamn C, Murray K, Bockenstedt L, Kerwin M, Reed E, Harris E, Stuart K, Peters B, Sesma A, Montgomery R, Sarwal M. Proteome Analysis for Inflammation Related to Acute and Convalescent Infection. Inflammation 2023, 47: 346-362. PMID: 37831367, PMCID: PMC10799112, DOI: 10.1007/s10753-023-01913-3.Peer-Reviewed Original ResearchC motif chemokine ligand 1C motif chemokine receptor 7Human Immunology Project ConsortiumWest Nile virusDengue virusLyme diseaseKidney transplant patientsChemokine ligand 1Chemokine receptor 7Common therapeutic interventionTumor necrosis factor receptorHost defense mechanismsNecrosis factor receptorCell surface markersConvalescent infectionTransplant patientsConvalescent phaseImmune signaturesAcute phaseConvalescent stageReceptor 7Common biological pathwaysHealthy donorsPolyomavirus infectionImmune responseMulti-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Diray-Arce J, Fourati S, Jayavelu N, Patel R, Maguire C, Chang A, Dandekar R, Qi J, Lee B, van Zalm P, Schroeder A, Chen E, Konstorum A, Brito A, Gygi J, Kho A, Chen J, Pawar S, Gonzalez-Reiche A, Hoch A, Milliren C, Overton J, Westendorf K, Network I, Abraham J, Adkisson M, Albert M, Torres L, Alvarenga B, Anderson M, Anderson E, Arnett A, Asashima H, Atkinson M, Baden L, Barton B, Beach K, Beagle E, Becker P, Bell M, Bernui M, Bime C, Kumar A, Booth L, Borresen B, Brakenridge S, Bristow L, Bryant R, Calfee C, Manuel J, Carrillo S, Chak S, Chang I, Connors J, Conway M, Corry D, Cowan D, Croen B, Dela Cruz C, Cusimano G, Eaker L, Edwards C, Ehrlich L, Elashoff D, Erickson H, Erle D, Farhadian S, Farrugia K, Fatou B, Fernandes A, Fernandez-Sesma A, Fragiadakis G, Furukawa S, Geltman J, Ghale R, Bermúdez M, Goonewardene M, Sanchez E, Guirgis F, Hafler D, Hamilton S, Harris P, Nemati A, Hendrickson C, Agudelo N, Hodder T, Holland S, Hough C, Huerta C, Hurley K, Hutton S, Iwasaki A, Jauregui A, Jha M, Johnson B, Joyner D, Kangelaris K, Kelly G, Khalil Z, Khan Z, Kheradmand F, Kim J, Kimura H, Ko A, Kohr B, Kraft M, Krummel M, Kutzler M, Lasky-Su J, Lee S, Lee D, Leipold M, Lentucci C, Leroux C, Lin E, Liu S, Love C, Lu Z, Maliskova L, Roth B, Manohar M, Martens M, McComsey G, McEnaney K, McLin R, Melamed E, Melnyk N, Mendez K, Messer W, Metcalf J, Michelotti G, Mick E, Mohanty S, Mosier J, Mulder L, Murphy M, Nadeau K, Nelson E, Nelson A, Nguyen V, Oberhaus J, Panganiban B, Pellegrini K, Pickering H, Powell D, Presnell S, Pulendran B, Rahman A, Sadeed A, Raskin A, Reed E, Pereira S, Rivera A, Rogers J, Rogers A, Rogowski B, Rooks R, Rosenberg-Hasson Y, Rothman J, Rousseau J, Salehi-Rad R, Saluvan M, Samaha H, Schaenman J, Schunk R, Semenza N, Sen S, Sevransky J, Seyfert-Margolis V, Shaheen T, Shaw A, Sieg S, Siegel S, Sigal N, Siles N, Simmons B, Simon V, Singh G, Sinko L, Smith C, Smolen K, Song L, Srivastava K, Sullivan P, Syphurs C, Tcheou J, Tegos G, Tharp G, Ally A, Tsitsiklis A, Ungaro R, Vaysman T, Viode A, Vita R, Wang X, Ward A, Ward D, Willmore A, Woloszczuk K, Wong K, Woodruff P, Xu L, van Haren S, van de Guchte A, Zhao Y, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, Grubaugh N, van Bakel H, Wilson M, Rajan J, Steen H, Eckalbar W, Cotsapas C, Langelier C, Levy O, Altman M, Maecker H, Montgomery R, Haddad E, Sekaly R, Esserman D, Ozonoff A, Becker P, Augustine A, Guan L, Peters B, Kleinstein S. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients. Cell Reports Medicine 2023, 4: 101079. PMID: 37327781, PMCID: PMC10203880, DOI: 10.1016/j.xcrm.2023.101079.Peer-Reviewed Original ResearchConceptsDisease courseFatal COVID-19 diseaseHospitalized COVID-19 patientsSevere disease courseCOVID-19 participantsCOVID-19 patientsTrajectory groupsHost immune responseCOVID-19 diseaseImmune correlatesAcute infectionClinical courseHospital admissionClinical outcomesFatal outcomeClinical prognosisImmune responseSevere diseaseLongitudinal bloodNasal samplesBiologic stateLongitudinal studyDistinct assaysCohortMolecular signaturesPlatelet 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 participantsPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2022
Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease
Cahill M, Montgomery R. Analytical Approaches to Uncover Genetic Associations for Rare Outcomes: Lessons from West Nile Neuroinvasive Disease. Methods In Molecular Biology 2022, 2585: 193-203. PMID: 36331775, PMCID: PMC9867870, DOI: 10.1007/978-1-0716-2760-0_17.Peer-Reviewed Original ResearchConceptsWest Nile neuroinvasive diseaseNeuroinvasive diseaseViral infectionWest Nile viral infectionSevere neuroinvasive diseaseMore severe outcomesGenetic factorsRare outcomesLimited cohort sizeSevere West Nile neuroinvasive diseaseWest Nile infectionVector-borne viral infectionSevere outcomesImmune responseSevere diseaseHigh riskFatal diseaseVaccine developmentInfectionDiseaseInfected humansWest NileSerious diseaseOutcomesCohort sizeSingle-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
Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study
, , Rouphael N, Maecker H, Montgomery R, Diray-Arce J, Kleinstein S, Altman M, Bosinger S, Eckalbar W, Guan L, Hough C, Krammer F, Langelier C, Levy O, McEnaney K, Peters B, Rahman A, Rajan J, Sigelman S, Steen H, van Bakel H, Ward A, Wilson M, Woodruff P, Zamecnik C, Augustine A, Ozonoff A, Reed E, Becker P, Higuita N, Altman M, Atkinson M, Baden L, Becker P, Bime C, Brakenridge S, Calfee C, Cairns C, Corry D, Davis M, Augustine A, Ehrlich L, Haddad E, Erle D, Fernandez-Sesma A, Hafler D, Hough C, Kheradmand F, Kleinstein S, Kraft M, Levy O, McComsey G, Melamed E, Messer W, Metcalf J, Montgomery R, Nadeau K, Ozonoff A, Peters B, Pulendran B, Reed E, Rouphael N, Sarwal M, Schaenman J, Sekaly R, Shaw A, Simon V. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study. Science Immunology 2021, 6: eabf3733. PMID: 34376480, PMCID: PMC8713959, DOI: 10.1126/sciimmunol.abf3733.Peer-Reviewed Original ResearchConceptsCOVID-19 cohortProspective longitudinal studyHost immune responseLongitudinal studyCOVID-19Identification of biomarkersHospitalized patientsRespiratory secretionsClinical criteriaDisease progressionImmune responseRadiographic dataImmunologic assaysEffective therapeuticsOptimal timingStudy designBiologic samplingSuch interventionsCohortSeveritySample collectionAssay protocolsPatientsSingle cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signsDesign and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder
Biondi BE, Mohanty S, Wyk BV, Montgomery RR, Shaw AC, Springer SA. Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder. Contemporary Clinical Trials Communications 2021, 21: 100704. PMID: 33490708, PMCID: PMC7807244, DOI: 10.1016/j.conctc.2021.100704.Peer-Reviewed Original ResearchOpioid use disorderProspective cohort studyHIV infectionCohort studyMedication treatmentUse disordersDSM-5 opioid-use disordersLongitudinal studyBiological effectsHIV continuumMonth 6Immune responseDifferential biological effectsMOUDHIVSystems biology approachInfectionTreatmentDSM-5DisordersPersonsBiology approachMedicationsBuprenorphineMethadone
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 dysregulation
2019
Exploring single-cell data with deep multitasking neural networks
Amodio M, van Dijk D, Srinivasan K, Chen WS, Mohsen H, Moon KR, Campbell A, Zhao Y, Wang X, Venkataswamy M, Desai A, Ravi V, Kumar P, Montgomery R, Wolf G, Krishnaswamy S. Exploring single-cell data with deep multitasking neural networks. Nature Methods 2019, 16: 1139-1145. PMID: 31591579, PMCID: PMC10164410, DOI: 10.1038/s41592-019-0576-7.Peer-Reviewed Original ResearchElevated 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
2018
Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis
Cahill ME, Conley S, DeWan AT, Montgomery RR. Identification of genetic variants associated with dengue or West Nile virus disease: a systematic review and meta-analysis. BMC Infectious Diseases 2018, 18: 282. PMID: 29929468, PMCID: PMC6014009, DOI: 10.1186/s12879-018-3186-6.Peer-Reviewed Original ResearchConceptsWest Nile virus diseaseSevere diseaseVirus diseaseWest Nile virus infectionGenetic factorsGenetic variantsSevere disease outcomesPotential therapeutic interventionsGenetic risk factorsAdditional genetic factorsWest Nile virusMinority of individualsSymptomatic infectionAsymptomatic infectionMechanisms of resistanceRisk factorsImmune mechanismsInitial symptomsDisease outcomeVirus infectionImmune responseDengue diseaseDisease pathogenesisTherapeutic interventionsSystematic reviewSIRT6 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 severityP65SIRT6CytokinesVirusAge-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes
Wang X, Malawista A, Qian F, Ramsey C, Allore HG, Montgomery RR. Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes. Oncotarget 2018, 9: 9572-9580. PMID: 29515754, PMCID: PMC5839385, DOI: 10.18632/oncotarget.23851.Peer-Reviewed Original ResearchReceptor-mediated immune responsesChronic tissue inflammationAge-dependent differencesAge-related changesImmune deteriorationChronic inflammationTissue inflammationTAM receptorsImmune responseImmune stimulationInflammatory regulatorsTAM familyComplex dysregulationInflammationReceptor tyrosine kinasesOlder adultsElevated expressionCytokine receptorsMonocytesReceptorsTyrosine kinaseMediator AktNegative regulatorResponseExpression
2017
Reduced 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 ResearchConceptsInnate 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
2016
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis
Lindow JC, Wunder EA, Popper SJ, Min JN, Mannam P, Srivastava A, Yao Y, Hacker KP, Raddassi K, Lee PJ, Montgomery RR, Shaw AC, Hagan JE, Araújo GC, Nery N, Relman DA, Kim CC, Reis MG, Ko AI. Cathelicidin Insufficiency in Patients with Fatal Leptospirosis. PLOS Pathogens 2016, 12: e1005943. PMID: 27812211, PMCID: PMC5094754, DOI: 10.1371/journal.ppat.1005943.Peer-Reviewed Original ResearchConceptsHost immune responseHigh bacterial loadBacterial loadAcute leptospirosisCase fatalityFatal casesDisease progressionImmune responseHigher systemic bacterial loadsValuable new therapeutic approachPro-inflammatory cytokine receptorsAdaptive immune signaturesSystemic bacterial loadsIndependent risk factorTime of hospitalizationDuration of illnessHigh case fatalityPoor clinical outcomeNew therapeutic approachesBlood transcriptional profilingLimited study sizeFatal leptospirosisLethal leptospirosisRANTES levelsSerum cathelicidinRole 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 susceptibilityDysregulation
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 ResearchConceptsImmune responseInnate immune changesInnate immune responseCytokine levelsInappropriate elevationImmune changesNaïve cell populationT cellsAdaptive immunityViral infectionParadoxical increaseInnate immunityMultiple cell typesParadoxical changesCell populationsActivation stateImmunityCell typesSevere consequencesResponseTissue contextImmunosenescenceVaccinationPopulationInfection