2022
Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvant
2021
B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma
Ohm-Laursen L, Meng H, Hoehn KB, Nouri N, Jiang Y, Clouser C, Johnstone TG, Hause R, Sandhar BS, Upton NEG, Chevretton EB, Lakhani R, Corrigan CJ, Kleinstein SH, Gould HJ. B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma. Frontiers In Immunology 2021, 12: 702074. PMID: 34721376, PMCID: PMC8552043, DOI: 10.3389/fimmu.2021.702074.Peer-Reviewed Original ResearchConceptsLower respiratory tractRespiratory tractB cellsAtopic asthmaPlasma cellsCommon respiratory tract diseaseB-cell mobilizationNon-atopic controlsRespiratory tract mucosaUpper respiratory tractRespiratory tract diseaseOrgan-specific diseasesAntibody repertoireB cell clonesAdaptive immune receptor repertoire sequencingBronchial mucosaNasal mucosaTract diseaseCell mobilizationIsotype selectionAntigen specificityAdult volunteersMucosal surfacesImmune systemAsthmaMind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases
D'Souza MP, Palin AC, Calder T, Golding H, Kleinstein SH, Milliken EL, O'Connor D, Tomaras G, Warren J, Boggiano C. Mind the gap from research laboratory to clinic: Challenges and opportunities for next-generation assays in human diseases. Vaccine 2021, 39: 5233-5239. PMID: 34366145, PMCID: PMC8343370, DOI: 10.1016/j.vaccine.2021.07.071.Peer-Reviewed Original ResearchConceptsNext-generation assaysSevere acute respiratory syndrome coronavirus type 2Human immunodeficiency virusCoronavirus type 2National InstituteVaccine delivery methodNovel animal modelProtective immunityImmunodeficiency virusLicensed vaccineEffective vaccineModern vaccinologyPowerful adjuvantAnimal modelsImproved vaccinesType 2Immune systemImmunogen designVaccine developmentInfectious diseasesVaccineGeneration assaysTuberculosisDiseaseCritical pathogens
2016
Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells
Rubelt F, Bolen CR, McGuire HM, Heiden J, Gadala-Maria D, Levin M, M. Euskirchen G, Mamedov MR, Swan GE, Dekker CL, Cowell LG, Kleinstein SH, Davis MM. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells. Nature Communications 2016, 7: 11112. PMID: 27005435, PMCID: PMC5191574, DOI: 10.1038/ncomms11112.Peer-Reviewed Original ResearchConceptsChromosome-wide levelJ gene segmentsAntigen receptor repertoireHeritable mechanismsSingle chromosomeEpigenetic differencesHeritable differencesReceptor repertoireLymphocyte receptor repertoireGene segmentsAdaptive immune systemHeritable factorsRepertoireRelative usageAntigen-experienced cellsThymic selectionCellsImmune systemChromosomesSignificant variationCDR3 regionMonozygotic twinsRearrangementT lymphocyte subsets
2015
Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases
Gorenshteyn D, Zaslavsky E, Fribourg M, Park CY, Wong AK, Tadych A, Hartmann BM, Albrecht RA, García-Sastre A, Kleinstein SH, Troyanskaya OG, Sealfon SC. Interactive Big Data Resource to Elucidate Human Immune Pathways and Diseases. Immunity 2015, 43: 605-614. PMID: 26362267, PMCID: PMC4753773, DOI: 10.1016/j.immuni.2015.08.014.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsBayes TheoremComputational BiologyGene Regulatory NetworksHost-Pathogen InteractionsHumansImmune SystemImmune System DiseasesInternetProtein Interaction MappingProtein Interaction MapsReproducibility of ResultsSignal TransductionSupport Vector MachineTranscriptomeVirus DiseasesConceptsPublic high-throughput dataGenome-scale experimentsDisease-associated genesHigh-throughput datasetsHigh-throughput dataData-driven hypothesesGenetic studiesImmune pathwaysGenesImmunological diseasesFunctional relationshipBiomedical research effortsImportant interactionsMolecular entitiesImmune systemHuman immune systemProteinExponential growthPathwayData resourcesBayesian integrationRelevant insightsGrowthCompendiumIdentificationAnalysis of gene–environment interactions in postnatal development of the mammalian intestine
Rakoff-Nahoum S, Kong Y, Kleinstein SH, Subramanian S, Ahern PP, Gordon JI, Medzhitov R. Analysis of gene–environment interactions in postnatal development of the mammalian intestine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1929-1936. PMID: 25691701, PMCID: PMC4343130, DOI: 10.1073/pnas.1424886112.Peer-Reviewed Original ResearchConceptsTLR/IL-1RToll-like receptorsPostnatal developmentIntestinal gene expressionMyeloid differentiation factor 88Domain-containing adapter-inducing interferonDifferentiation factor 88Adapter-inducing interferonMast cell homeostasisIntestinal ontogenyReceptor family membersFactor 88WT miceGene expression programsSmooth muscle developmentGene-environment interactionsIL-1RIntestinal physiologyImmune systemKnockout littermatesPostnatal transitionMicrobial colonizationIntestinal contentsGene expressionPubertal maturation
2014
High-resolution antibody dynamics of vaccine-induced immune responses
Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Heiden J, Kelton W, Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM. High-resolution antibody dynamics of vaccine-induced immune responses. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 4928-4933. PMID: 24639495, PMCID: PMC3977259, DOI: 10.1073/pnas.1323862111.Peer-Reviewed Original Research
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
2009
Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells
Bruno VM, Hannemann S, Lara-Tejero M, Flavell RA, Kleinstein SH, Galán JE. Salmonella Typhimurium Type III Secretion Effectors Stimulate Innate Immune Responses in Cultured Epithelial Cells. PLOS Pathogens 2009, 5: e1000538. PMID: 19662166, PMCID: PMC2714975, DOI: 10.1371/journal.ppat.1000538.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsBlotting, WesternCell LineColitisEpithelial CellsGene ExpressionGene Expression ProfilingGuanine Nucleotide Exchange FactorsHumansImmunity, InnateMiceMitogen-Activated Protein Kinase KinasesMyotonin-Protein KinaseNF-kappa BOligonucleotide Array Sequence AnalysisProtein Serine-Threonine KinasesReverse Transcriptase Polymerase Chain ReactionSalmonella InfectionsSalmonella typhimuriumSignal TransductionTranscription, GeneticConceptsInnate immune receptorsInnate immune responseIntestinal inflammationImmune responseEpithelial cellsBacterial productsIntestinal inflammatory pathologyImmune receptorsCultured epithelial cellsEnteric pathogen Salmonella typhimuriumInnate immune systemIntestinal epithelial cellsInflammatory pathologyInflammatory responseType III secretion effectorsImmune systemSalmonella typhimuriumNF-kappaBMitogen-activated protein kinaseEnteric pathogensPathogen Salmonella typhimuriumPathologyReceptorsInflammationType III secretion system