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