2023
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.Peer-Reviewed Original ResearchConceptsMild COVID-19Control individualsInnate immune genesInfluenza vaccinationCOVID-19Day 28Day 1Viral infectionNon-hospitalized COVID-19Baseline immune statusAcute viral infectionSex-matched control individualsMemory-like CD8IL-15 responsesIL-15 stimulationSex-dimorphic effectsToll-like receptorsFuture immune responseHealthy control individualsImmune genesSystems immunology approachT-cell activation signaturesHealthy male individualsMale individualsMore IFNγ
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 driversTime-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
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 vaccineBroad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus
Kotliarov Y, Sparks R, Martins A, Mulè M, Lu Y, Goswami M, Kardava L, Banchereau R, Pascual V, Biancotto A, Chen J, Schwartzberg P, Bansal N, Liu C, Cheung F, Moir S, Tsang J. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nature Medicine 2020, 26: 618-629. PMID: 32094927, PMCID: PMC8392163, DOI: 10.1038/s41591-020-0769-8.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdolescentAdultAgedAged, 80 and overAntibody FormationB-LymphocytesChildChild, PreschoolCohort StudiesFemaleGene Expression ProfilingHumansInfluenza VaccinesInfluenza, HumanLupus Erythematosus, SystemicMaleMiddle AgedTranscriptomeVaccinationYellow FeverYellow Fever VaccineYoung AdultConceptsDisease activityVaccine responsivenessAutoimmune disease activityBlood transcriptional signaturesYellow fever vaccinationSystemic lupus erythematosusClinical quiescenceFever vaccinationLupus erythematosusCancer immunotherapyBaseline predictorsDisease outcomeHealthy subjectsImmune responseI IFNHealthy individualsVaccinationTranscriptional signatureImmune variationBaseline statePatientsExtent of activationBiological basisSurface proteinsInfection response
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 responseCD19
2017
Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria
Matsuyama M, Martins A, Shallom S, Kamenyeva O, Kashyap A, Sampaio E, Kabat J, Olivier K, Zelazny A, Tsang J, Holland S. Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 241-252. PMID: 28915071, PMCID: PMC5806000, DOI: 10.1165/rcmb.2017-0218oc.Peer-Reviewed Original ResearchConceptsCholesterol biosynthesisUpregulation of genesRespiratory epitheliumGene expression signaturesCiliary genesTranscriptional responseRNA sequencingEpithelial cell infectionResponse genesInflammatory response genesHost responseCytokine/chemokine productionRespiratory epithelial cell culturesEpithelial cell culturesPulmonary nontuberculous mycobacteria (NTM) diseaseExpression signaturesMajor host responsesCytokines/chemokinesGenesRespiratory epithelial cellsCiliary functionNontuberculous mycobacteria diseaseCell infectionMultiplicity of infectionBiosynthesis
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-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK Pathways
Yeganegi M, Leung C, Martins A, Kim S, Reid G, Challis J, Bocking A. Lactobacillus rhamnosus GR-1-Induced IL-10 Production in Human Placental Trophoblast Cells Involves Activation of JAK/STAT and MAPK Pathways. Reproductive Sciences 2010, 17: 1043-1051. PMID: 20858906, DOI: 10.1177/1933719110377237.Peer-Reviewed Original ResearchConceptsHuman placental trophoblast cellsPlacental trophoblast cellsPreterm birthEnzyme-linked immunosorbent assayRhamnosus GR-1Gr-1Trophoblast cellsIntrauterine infection/inflammationAnti-inflammatory effectsIL-10 productionInfection/inflammationWestern blot analysisHealthy pregnancyPhosphorylation of STAT3IL-10Janus kinase/signal transducerJAK/STATCytokine regulationKinase/signal transducerPotential preventionPlacental trophoblastsMitogen-activated protein kinase pathwayAbsence of pretreatmentHuman placentaSTAT-3Lactobacillus 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