Featured Publications
Benchmarking transcriptional host response signatures for infection diagnosis
Chawla D, Cappuccio A, Tamminga A, Sealfon S, Zaslavsky E, Kleinstein S. Benchmarking transcriptional host response signatures for infection diagnosis. Cell Systems 2022, 13: 974-988.e7. PMID: 36549274, PMCID: PMC9768893, DOI: 10.1016/j.cels.2022.11.007.Peer-Reviewed Original ResearchConceptsInfection diagnosisHost response signatureNon-infectious conditionsClinical applicationResponse signatureChronic infectionPathogen of interestBacterial infectionsInfectionSignature of infectionDisease signaturesDiagnosisTranscriptional profilesStandardized methodologyDevelopment of signaturesDecreased performance
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 virusPD-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
2021
Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses
Nudelman I, Kudrin D, Nudelman G, Deshpande R, Hartmann BM, Kleinstein SH, Myers CL, Sealfon SC, Zaslavsky E. Comparing Host Module Activation Patterns and Temporal Dynamics in Infection by Influenza H1N1 Viruses. Frontiers In Immunology 2021, 12: 691758. PMID: 34335598, PMCID: PMC8317020, DOI: 10.3389/fimmu.2021.691758.Peer-Reviewed Original ResearchConceptsDifferent virus strainsHost responseVirus strainsInfluenza virus infectionSerious global health threatInfluenza H1N1 virusCommon core responseGlobal health threatH1N1 virusVirus infectionImmune responseInfluenza strainsTherapeutic targetInfluenza virusHealth threatInfectionActivation patternsDifferent virusesDifferent temporal patternsVirusHost cellsFunctional networksFunctional pathwaysSame cellular pathwaysCellular pathways
2020
A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection
Alsoussi WB, Turner JS, Case JB, Zhao H, Schmitz AJ, Zhou JQ, Chen RE, Lei T, Rizk AA, McIntire KM, Winkler ES, Fox JM, Kafai NM, Thackray LB, Hassan AO, Amanat F, Krammer F, Watson CT, Kleinstein SH, Fremont DH, Diamond MS, Ellebedy AH. A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. The Journal Of Immunology 2020, 205: ji2000583. PMID: 32591393, PMCID: PMC7566074, DOI: 10.4049/jimmunol.2000583.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralBetacoronavirusChlorocebus aethiopsCoronavirus InfectionsCOVID-19Disease Models, AnimalEpitope MappingFemaleHEK293 CellsHumansImmunodominant EpitopesMiceMice, Inbred C57BLPandemicsPeptidyl-Dipeptidase APneumonia, ViralProtein Interaction Domains and MotifsSARS-CoV-2Spike Glycoprotein, CoronavirusTransfectionVero CellsConceptsSARS-CoV-2 infectionSARS-CoV-2Receptor-binding domainSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Angiotensin-converting enzyme 2Human angiotensin-converting enzyme 2Wild-type SARS-CoV-2Lung viral loadsSyndrome coronavirus 2Millions of infectionsTrimeric spike glycoproteinLicensed therapeuticsViral loadCoronavirus 2Systemic disseminationEffective antiviralsEnzyme 2Murine modelMurine mAbsEffective interventionsInfectionWeight lossSpike glycoprotein
2015
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses
Hartmann BM, Thakar J, Albrecht RA, Avey S, Zaslavsky E, Marjanovic N, Chikina M, Fribourg M, Hayot F, Schmolke M, Meng H, Wetmur J, García-Sastre A, Kleinstein SH, Sealfon SC. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses. Journal Of Virology 2015, 89: 10190-10205. PMID: 26223639, PMCID: PMC4580178, DOI: 10.1128/jvi.01523-15.Peer-Reviewed Original ResearchMeSH KeywordsAntigenic VariationDendritic CellsEuropeGene Expression ProfilingGene Expression RegulationHistory, 20th CenturyHistory, 21st CenturyHost-Pathogen InteractionsHumansInfluenza A Virus, H1N1 SubtypeInfluenza Pandemic, 1918-1919Influenza, HumanInterferonsMolecular EpidemiologyNF-kappa BPandemicsReassortant VirusesRecombination, GeneticSeasonsSignal TransductionTime FactorsUnited StatesConceptsHuman dendritic cellsDendritic cellsImmune responseInfluenza virusSeasonal strainsNF-κBSeasonal H1N1 influenza virusHuman influenza virus infectionH1N1 influenza strainInterferon-stimulated gene responseSeasonal influenza virusesInfluenza virus infectionH1N1 influenza virusStrain-dependent differencesClinical severityVirus infectionInfluenza strainsAntiviral programViral infectionPandemic strainsHost responseAntigenic driftInfectionH postinfectionSelective inductionSalmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation
Di Niro R, Lee SJ, Vander Heiden J, Elsner RA, Trivedi N, Bannock JM, Gupta NT, Kleinstein SH, Vigneault F, Gilbert TJ, Meffre E, McSorley SJ, Shlomchik MJ. Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation. Immunity 2015, 43: 120-131. PMID: 26187411, PMCID: PMC4523395, DOI: 10.1016/j.immuni.2015.06.013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalB-LymphocytesClonal Selection, Antigen-MediatedGerminal CenterImmunoglobulin GLymphocyte ActivationMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutReceptors, Antigen, B-CellSalmonella InfectionsSalmonella typhimuriumSomatic Hypermutation, ImmunoglobulinSpleenConceptsB cell receptorExtrafollicular sitesGerminal centersAffinity maturationInfection of miceB cell responsesB cell activationDetectable antibodiesSomatic hypermutationExtrafollicular responseAntigen microarraysSalmonella infectionAntigen targetsCell activationSalmonella typhimuriumCell responsesBCR specificityFlow cytometryCell receptorMonoclonal antibodiesUndetectable affinityClonal selectionInfectionAntibodiesLaser microdissection
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 cellsImmune 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
Overcoming NS1-Mediated Immune Antagonism Involves Both Interferon-Dependent and Independent Mechanisms
Thakar J, Schmid S, Duke JL, García-Sastre A, Kleinstein SH. Overcoming NS1-Mediated Immune Antagonism Involves Both Interferon-Dependent and Independent Mechanisms. Journal Of Interferon & Cytokine Research 2013, 33: 700-708. PMID: 23772952, PMCID: PMC3814816, DOI: 10.1089/jir.2012.0113.Peer-Reviewed Original ResearchConceptsNonstructural protein 1Immune antagonismWild-type C57BL/6 miceIFN-independent mechanismsInduction of IFNCritical antiviral cytokinesInduction of IFNB1Host interferon responseEffective IFNInterferon-DependentC57BL/6 miceAntiviral cytokinesInfluenza A.IFNImmune systemInterferon responseFlu strainImmune antagonistsProtein 1H postinfectionIndependent mechanismsInfectionMiceAntagonismIFNB1
2011
Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4+ Cell Properties during Viral Infection
Marshall HD, Chandele A, Jung YW, Meng H, Poholek AC, Parish IA, Rutishauser R, Cui W, Kleinstein SH, Craft J, Kaech SM. Differential Expression of Ly6C and T-bet Distinguish Effector and Memory Th1 CD4+ Cell Properties during Viral Infection. Immunity 2011, 35: 633-646. PMID: 22018471, PMCID: PMC3444169, DOI: 10.1016/j.immuni.2011.08.016.Peer-Reviewed Original ResearchConceptsAcute viral infectionViral infectionEffector cellsTfh cell markersVirus-specific effectorT helper 1Th1 effector cellsT-bet expressionIL-7R expressionMemory precursor cellsTh1 CD4Helper 1Memory TTh1 cellsProliferative responseSecondary infectionEffector typeReliable markerCell markersInfectionPrecursor cellsGene expression profilesLy6CCell featuresCell developmentPS2-108. Infection with Hepatitis C down-regulates the expression of cytokine genes in peripheral blood
Taylor M, Bolen C, Kleinstein S, Brodsky L. PS2-108. Infection with Hepatitis C down-regulates the expression of cytokine genes in peripheral blood. Cytokine 2011, 56: 94. DOI: 10.1016/j.cyto.2011.07.274.Peer-Reviewed Original Research