2019
IFN-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
2017
Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network
Martins A, Narayanan M, Prüstel T, Fixsen B, Park K, Gottschalk R, Lu Y, Andrews-Pfannkoch C, Lau W, Wendelsdorf K, Tsang J. Environment Tunes Propagation of Cell-to-Cell Variation in the Human Macrophage Gene Network. Cell Systems 2017, 4: 379-392.e12. PMID: 28365150, PMCID: PMC8392141, DOI: 10.1016/j.cels.2017.03.002.Peer-Reviewed Original ResearchConceptsGene networksCellular adaptationCell variationSingle-cell transcriptomic studiesGene-gene correlationsUnderlying regulatory mechanismsDegree of phosphorylationPhenotypic diversityTranscriptomic studiesEnvironmental adaptationMultiple molecular parametersGene expressionRegulatory mechanismsCellular heterogeneityDistinct environmentsSingle cellsHuman macrophagesQuantitative tuningCell populationsNatural perturbationsGenesDifferent environmentsSuch variationCellsStochastic simulation analysis
2016
Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling
Narayanan M, Martins A, Tsang J. Robust Inference of Cell-to-Cell Expression Variations from Single- and K-Cell Profiling. PLOS Computational Biology 2016, 12: e1005016. PMID: 27438699, PMCID: PMC4954693, DOI: 10.1371/journal.pcbi.1005016.Peer-Reviewed Original ResearchConceptsSingle-cell expression levelsExpression levelsNovel biological informationSingle cellsKey inflammatory genesExpression variationGene expressionCellular heterogeneityBiological informationRandom poolSingle populationHuman macrophagesBiological conditionsCell populationsGenesMultiplexed technologiesK cellsInflammatory genesCellsBiological varianceQuantifying differencesSensitive technologyContinuous variationRobust inferenceProfilingDistinct 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
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
2008
Cathepsin 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