2023
Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites
Mura M, Misganaw B, Gautam A, Robinson T, Chaudhury S, Bansal N, Martins A, Tsang J, Hammamieh R, Bergmann-Leitner E. Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites. Human Vaccines & Immunotherapeutics 2023, 19: 2282693. PMID: 38010150, PMCID: PMC10760396, DOI: 10.1080/21645515.2023.2282693.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsNon-protected individualsHuman malaria infectionImmune correlatesMalaria infectionVaccine-induced responsesCorrelates of protectionTranscriptomic analysisBlood mononuclear cellsAntigen-specific stimulationTranscriptomic profilesAntigen-specific cellsWhole blood transcriptomic analysesImmune signaturesMalaria vaccineMononuclear cellsInfectious challengeVaccine platformEffective vaccineMosquito bitesLongitudinal time pointsSubunit vaccineInfectious pathogensTranscriptional eventsVaccine
2021
Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential
Rogers D, Sood A, Wang H, van Beek J, Rademaker T, Artusa P, Schneider C, Shen C, Wong D, Bhagrath A, Lebel M, Condotta S, Richer M, Martins A, Tsang J, Barreiro L, François P, Langlais D, Melichar H, Textor J, Mandl J. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential. Cell Reports 2021, 37: 110064. PMID: 34852223, DOI: 10.1016/j.celrep.2021.110064.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingGene expression differencesCell receptor signalingChromatin accessibilityLineage choiceTCR signal strengthCell chromatinTranscriptional differencesRNA sequencingExpression differencesReceptor signalingLandscape differencesEffector potentialEffector lineagesThymic developmentCellsNaive CD4Self-peptide MHCChromatinCognate antigenLineagesGenesSignalingTCR interactionsKey drivers
2020
Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells
Baharom F, Ramirez-Valdez RA, Tobin KKS, Yamane H, Dutertre CA, Khalilnezhad A, Reynoso GV, Coble VL, Lynn GM, Mulè MP, Martins AJ, Finnigan JP, Zhang XM, Hamerman JA, Bhardwaj N, Tsang JS, Hickman HD, Ginhoux F, Ishizuka AS, Seder RA. Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells. Nature Immunology 2020, 22: 41-52. PMID: 33139915, PMCID: PMC7746638, DOI: 10.1038/s41590-020-00810-3.Peer-Reviewed Original ResearchConceptsNeoantigen-specific CD8T cellsToll-like receptor 7/8 agonistQuality of CD8Stem-like TCF1T cell immunityStem-like CD8Superior antitumor responsesPersonalized cancer vaccinesStem-like genesStem-like cellsIntravenous vaccinationNanoparticle vaccinationAntitumor immunityCheckpoint blockadeCell immunityDendritic cellsAntitumor responseEffector cellsSubcutaneous immunizationCancer vaccinesVaccine parametersNeoantigen peptidesAntigen presentationNanoparticle vaccine
2019
Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells
Zhong C, Zheng M, Cui K, Martins A, Hu G, Li D, Tessarollo L, Kozlov S, Keller J, Tsang J, Zhao K, Zhu J. Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells. Immunity 2019, 52: 83-95.e4. PMID: 31882362, PMCID: PMC6962539, DOI: 10.1016/j.immuni.2019.12.001.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineageCells, CulturedGATA3 Transcription FactorInhibitor of Differentiation Protein 2Interleukin Receptor Common gamma SubunitMiceMice, Inbred C57BLMice, KnockoutNuclear Receptor Subfamily 1, Group F, Member 3Programmed Cell Death 1 ReceptorPromyelocytic Leukemia Zinc Finger ProteinStem CellsT-Lymphocyte SubsetsT-Lymphocytes, Helper-InducerConceptsILC progenitorsDifferential expressionTranscription factor PLZFTranscriptional regulator Id2Common progenitorLymphoid progenitorsGATA3 expressionConditional deletionProgenitorsPLZFInnate lymphoid cellsExpressionLymphoid tissue inducer cellsLymphoid cellsLTi cellsCellsGATA3FateTranscription factor RORγtILC subsetsLineagesTranscriptionId2DeletionHigh amountsIFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses
Gottschalk R, Dorrington M, Dutta B, Krauss K, Martins A, Uderhardt S, Chan W, Tsang J, Torabi-Parizi P, Fraser I, Germain R. IFN-mediated negative feedback supports bacteria class-specific macrophage inflammatory responses. ELife 2019, 8: e46836. PMID: 31385572, PMCID: PMC6684266, DOI: 10.7554/elife.46836.Peer-Reviewed Original ResearchConceptsContext-dependent regulationGram-positive speciesGram-negative bacteriaClass-specific mannerInflammatory responseRegulatory eventsMolecular mechanismsMacrophage inflammatory responseMouse macrophagesLigand pairsInnate immunityInflammatory cytokine productionMacrophage responseBacteriaRegulationSpecific pathogensIL-10Cytokine productionLung infectionProduction dynamicsInhibitory eventsSpeciesMacrophagesNegative feedbackInflammation dynamicsResident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage
Uderhardt S, Martins A, Tsang J, Lämmermann T, Germain R. Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage. Cell 2019, 177: 541-555.e17. PMID: 30955887, PMCID: PMC6474841, DOI: 10.1016/j.cell.2019.02.028.Peer-Reviewed Original ResearchConceptsTissue-resident macrophagesTissue homeostasisDiverse tissuesCell deathOrgan architectureIndividual cellsNeutrophil swarmsResident macrophagesDense swarmsLocal cell injuryIntravital imagingLocal disruptionParenchymal cell deathDynamic intravital imagingInescapable consequenceCell damageCell injuryHomeostasisMacrophagesCascadeInflammatory damageDamageCellsAccumulationDisruption
2018
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism
Mao K, Baptista A, Tamoutounour S, Zhuang L, Bouladoux N, Martins A, Huang Y, Gerner M, Belkaid Y, Germain R. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature 2018, 554: 255-259. PMID: 29364878, DOI: 10.1038/nature25437.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCD4-Positive T-LymphocytesEpithelial CellsGastrointestinal MicrobiomeHomeodomain ProteinsHomeostasisImmunity, InnateInflammationInterleukin-23InterleukinsIntestine, SmallLipid MetabolismLymphocyte ActivationLymphocytesMaleMiceMonocytesPhosphorylationReceptors, CCR2STAT3 Transcription FactorSymbiosisTh17 CellsT-Lymphocytes, RegulatoryWeaning
2016
Distinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory Responses
Gottschalk R, Martins A, Angermann B, Dutta B, Ng C, Uderhardt S, Tsang J, Fraser I, Meier-Schellersheim M, Germain R. Distinct NF-κB and MAPK Activation Thresholds Uncouple Steady-State Microbe Sensing from Anti-pathogen Inflammatory Responses. Cell Systems 2016, 2: 378-390. PMID: 27237739, PMCID: PMC4919147, DOI: 10.1016/j.cels.2016.04.016.Peer-Reviewed Original ResearchConceptsNF-κBMAPK activationInflammatory mediator productionSet of genesInnate immune response systemNF-κB signalingInnate immune systemSwitch-like mannerMacrophage functional responsesImmune response systemInflammatory mediatorsTLR4 ligandMediator productionInflammatory responseMicrobial stimuliInnate responseImmune systemMAPK signalingMacrophage primingLigand sensitivityHuman macrophagesInverse correlationInvasive pathogensSingle receptorGenes
2015
Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages
Meshkibaf S, Martins A, Henry G, Kim S. Protective role of G-CSF in dextran sulfate sodium-induced acute colitis through generating gut-homing macrophages. Cytokine 2015, 78: 69-78. PMID: 26687628, DOI: 10.1016/j.cyto.2015.11.025.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsCells, CulturedColitisDextran SulfateGranulocyte Colony-Stimulating FactorHomeostasisInterleukin-13Interleukin-1betaIntestinesLipopolysaccharidesMacrophage Colony-Stimulating FactorMacrophagesMiceNitric Oxide Synthase Type IIReceptors, Granulocyte Colony-Stimulating FactorTumor Necrosis Factor-alphaConceptsInducible nitric oxide synthaseBone marrow-derived macrophagesG-CSFMarrow-derived macrophagesColony-stimulating factorAcute colitisDextran sulfate sodium-induced acute colitisSeverity of colitisDextran sulfate sodiumReceptor-deficient miceGranulocyte colony-stimulating factorDeath ligand 2Function of neutrophilsNitric oxide synthaseTumor necrosis factorMacrophage colony-stimulating factorRegulatory macrophage markersAdoptive transferSulfate sodiumIL-1βImmune homeostasisOxide synthaseMacrophage markersNecrosis factorImmune regulation
2012
Recent progress using systems biology approaches to better understand molecular mechanisms of immunity
Gottschalk R, Martins A, Sjoelund V, Angermann B, Lin B, Germain R. Recent progress using systems biology approaches to better understand molecular mechanisms of immunity. Seminars In Immunology 2012, 25: 201-208. PMID: 23238271, PMCID: PMC3834012, DOI: 10.1016/j.smim.2012.11.002.Commentaries, Editorials and LettersConceptsSystems biology approachBiology approachSingle-cell measurement technologiesTranscriptional networksSpatial regulationHigh-throughput data acquisitionMolecular mechanismsComputational integrationImmune systemFeedback loopNovel perturbationRecent progressSignalingReductionist researchRegulationBroad rangePotential sourceFunctionResponse heterogeneity
2011
The anti-inflammatory role of granulocyte colony-stimulating factor in macrophage–dendritic cell crosstalk after Lactobacillus rhamnosus GR-1 exposure
Martins A, Spanton S, Sheikh H, Kim S. The anti-inflammatory role of granulocyte colony-stimulating factor in macrophage–dendritic cell crosstalk after Lactobacillus rhamnosus GR-1 exposure. Journal Of Leukocyte Biology 2011, 89: 907-915. PMID: 21385950, DOI: 10.1189/jlb.0810445.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCulture Media, ConditionedCytokinesDendritic CellsEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGranulocyte Colony-Stimulating FactorInterleukin-12Interleukin-23Lacticaseibacillus rhamnosusMacrophagesMaleMAP Kinase Kinase 4MiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutP38 Mitogen-Activated Protein KinasesPhosphorylationReceptors, Granulocyte Colony-Stimulating FactorReverse Transcriptase Polymerase Chain ReactionRNA, MessengerConceptsIL-12 productionG-CSFIL-12P40 productionGr-1T cell stimulatory capacityIL-12/23 p40Cell stimulatory capacityAnti-inflammatory roleGranulocyte colony-stimulating factorCostimulatory molecules CD80Antibody-mediated neutralizationInnate immune systemColony-stimulating factorResponse of DCsSplenic DCsIL-23Cytokine profileStimulatory capacityIL-6Immune responseP40 subunitCell crosstalkP40 responseRG-CSF
2010
The multifaceted effects of granulocyte colony‐stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis
Martins A, Han J, Kim S. The multifaceted effects of granulocyte colony‐stimulating factor in immunomodulation and potential roles in intestinal immune homeostasis. IUBMB Life 2010, 62: 611-617. PMID: 20681025, PMCID: PMC2916186, DOI: 10.1002/iub.361.Commentaries, Editorials and LettersMeSH KeywordsAnimalsGranulocyte Colony-Stimulating FactorHomeostasisHumansImmunomodulationIntestinesConceptsColony-stimulating factorIntestinal immune homeostasisGranulocyte colony-stimulating factorImmune homeostasisMacrophage colony-stimulating factorG-CSFLocal immune homeostasisEndogenous G-CSFPotential roleMonocytes/macrophagesExogenous G-CSFGranulocyte/macrophage colony-stimulating factorDendritic cellsImmunosuppressive effectsImmunomodulatory effectsImmune cellsT lymphocytesImmune functionGM-CSFMyeloid hematopoiesisM-CSFImmunomodulationHomeostasisCellsFactors
2008
Reduced Expression of Basal and Probiotic-inducible G-CSF in Intestinal Mononuclear Cells Is Associated with Inflammatory Bowel Disease
Martins A, Colquhoun P, Reid G, Kim S. Reduced Expression of Basal and Probiotic-inducible G-CSF in Intestinal Mononuclear Cells Is Associated with Inflammatory Bowel Disease. Inflammatory Bowel Diseases 2008, 15: 515-525. PMID: 19058228, DOI: 10.1002/ibd.20808.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsEscherichia coliGranulocyte Colony-Stimulating FactorHumansInflammatory Bowel DiseasesInterleukin-12Interleukin-23Intestinal MucosaLacticaseibacillus rhamnosusLeukocytes, MononuclearMiceMice, Inbred C57BLMucous MembraneProbioticsReceptors, Granulocyte Colony-Stimulating FactorTumor Necrosis Factor-alphaConceptsGranulocyte-colony stimulating factorInflammatory bowel diseaseHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsG-CSF productionIntestinal mononuclear cellsBlood mononuclear cellsMononuclear cellsRhamnosus GR-1L. rhamnosus GR-1IL-23Bowel diseaseIntestinal lamina propria mononuclear cellsGr-1Intestinal lamina propria cellsLamina propria mononuclear cellsNon-IBD patientsReceptor knockout miceReceptor-deficient miceProinflammatory cytokine productionLamina propria cellsBone marrow-derived macrophagesIntestinal tissue samplesMarrow-derived macrophagesG-CSF releaseCathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in Macrophages
Ha S, Martins A, Khazaie K, Han J, Chan B, Kim S. Cathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in Macrophages. The Journal Of Immunology 2008, 181: 690-697. PMID: 18566436, DOI: 10.4049/jimmunol.181.1.690.Peer-Reviewed Original ResearchConceptsPlasma membraneIntracellular cathepsin B activityCathepsin BCathepsin B activityMouse bone marrow-derived macrophagesGene identification methodsBone marrow-derived macrophagesMarrow-derived macrophagesB activityEctopic expressionLysosomal cysteine proteinasesInnate immune responsePosttranslational processingCysteine proteinasesTNF-alphaVesiclesKey mediatorMembranePotent proinflammatory cytokineLess TNF-alphaChronic inflammatory diseaseMacrophagesMutagenesisGFPMicrobes
2006
G‐CSF‐mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus‐induced suppression of TNF production in macrophages
Kim S, Sheikh H, Ha S, Martins A, Reid G. G‐CSF‐mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus‐induced suppression of TNF production in macrophages. Cellular Microbiology 2006, 8: 1958-1971. PMID: 16889627, DOI: 10.1111/j.1462-5822.2006.00763.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Marrow CellsCell LineCytokinesEnterococcus faecalisEscherichia coliGranulocyte Colony-Stimulating FactorHumansInterleukin-10JNK Mitogen-Activated Protein KinasesLacticaseibacillus rhamnosusMacrophage ActivationMacrophagesMacrophages, PeritonealMiceMice, Inbred C57BLP38 Mitogen-Activated Protein KinasesPhosphorylationProbioticsSignal TransductionSTAT3 Transcription FactorTumor Necrosis Factor-alphaConceptsGranulocyte-colony stimulating factorTNF productionL. rhamnosus GGGr-1Rhamnosus GGReceptor knockout miceAnti-inflammatory effectsMonocytic cell line THP-1Human monocytic cell line THP-1Cell line THP-1Lipopolysaccharide-activated macrophagesActivation of STAT3C-Jun N-terminal kinaseImmunomodulatory effectsTumor necrosisImmunomodulatory propertiesKnockout miceParacrine routeStimulating factorMacrophagesTHP-1Subsequent inhibitionMouse macrophagesCulture supernatantsNovo protein synthesis