2021
Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19
Liu C, Martins AJ, Lau WW, Rachmaninoff N, Chen J, Imberti L, Mostaghimi D, Fink DL, Burbelo PD, Dobbs K, Delmonte OM, Bansal N, Failla L, Sottini A, Quiros-Roldan E, Lee Han K, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS, , Rossi C, Su H, Kuhns D, Cohen J, Notarangelo L, Tsang J, , Abers M, Apps R, Bosticardo M, Milanez-Almeida P, Mulè M, Shaw E, Zhang Y, , Castelli F, Muiesan M, Tomasoni G, Scolari F, Tucci A. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell 2021, 184: 1836-1857.e22. PMID: 33713619, PMCID: PMC7874909, DOI: 10.1016/j.cell.2021.02.018.Peer-Reviewed Original ResearchConceptsFatal COVID-19Peripheral immune cellsPlasmacytoid dendritic cellsPost-symptom onsetCOVID-19 patientsCOVID-19Fatty acid metabolismGene expression signaturesNK cellsSymptom onsetDendritic cellsSevere patientsFatal outcomeImmune response variationCellular inflammationImmune cellsInflammatory responseCell receptor sequencesExtensive patientClinical monitoringTherapeutic interventionsCell activationDay 17Disease severitySigns of exhaustion
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19IFN-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 dynamics
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
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
Lactobacillus rhamnosus GR-1 Stimulates Colony-Stimulating Factor 3 (Granulocyte) (CSF3) Output in Placental Trophoblast Cells in a Fetal Sex-Dependent Manner1
Yeganegi M, Leung C, Martins A, Kim S, Reid G, Challis J, Bocking A. Lactobacillus rhamnosus GR-1 Stimulates Colony-Stimulating Factor 3 (Granulocyte) (CSF3) Output in Placental Trophoblast Cells in a Fetal Sex-Dependent Manner1. Biology Of Reproduction 2010, 84: 18-25. PMID: 20811016, PMCID: PMC4480822, DOI: 10.1095/biolreprod.110.085167.Peer-Reviewed Original ResearchConceptsPlacental trophoblast cellsTrophoblast cellsPreterm birthFetal sex-dependent mannerAnti-inflammatory effectsJanus kinaseSex-dependent mannerColony-stimulating factor 3Mitogen-activated protein kinase 14Western blot analysisPreterm laborPhosphorylation of STAT3Interleukin-10Bacterial vaginosisTherapeutic benefitFemale fetusesProtein kinase 14Placenta culturesAbsence of pretreatmentMAPK14 inhibitorSignal transducerTranscription 3Cell preparationsUnderlying mechanismBlot analysis
2009
Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor
Yeganegi M, Watson C, Martins A, Kim S, Reid G, Challis J, Bocking A. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. American Journal Of Obstetrics And Gynecology 2009, 200: 532.e1-532.e8. PMID: 19285652, DOI: 10.1016/j.ajog.2008.12.032.Peer-Reviewed Original ResearchMeSH KeywordsCells, CulturedCyclooxygenase 2CytokinesFemaleHumansHydroxyprostaglandin DehydrogenasesInterleukin-10Interleukin-1betaLacticaseibacillus rhamnosusLipopolysaccharidesMaleObstetric Labor, PrematurePregnancyProbioticsSex FactorsToll-Like Receptor 4TrophoblastsTumor Necrosis Factor-alphaVaginosis, BacterialConceptsToll-like receptor 4Prostaglandin-endoperoxide synthase 2Placental trophoblast cellsIL-10Prostaglandin dehydrogenaseTrophoblast cellsPreterm laborTNF-alphaMale placentasFetal sexOutput of cytokinesHuman placental trophoblast cellsTumor necrosis factorEffects of lipopolysaccharideLipopolysaccharide-induced cytokineEnzyme-linked immunosorbentStudent's t-testPreterm birthBacterial vaginosisIL-1betaReceptor 4Necrosis factorTherapeutic benefitFemale placentasMale fetuses
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