2022
Characterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2021
Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation
Tomlinson KL, Lung TWF, Dach F, Annavajhala MK, Gabryszewski SJ, Groves RA, Drikic M, Francoeur NJ, Sridhar SH, Smith ML, Khanal S, Britto CJ, Sebra R, Lewis I, Uhlemann AC, Kahl BC, Prince AS, Riquelme SA. Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation. Nature Communications 2021, 12: 1399. PMID: 33658521, PMCID: PMC7930111, DOI: 10.1038/s41467-021-21718-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBiofilmsBronchoalveolar Lavage FluidCarbohydrate MetabolismCystic FibrosisGene Expression Regulation, BacterialGlycolysisHost-Pathogen InteractionsHumansHydro-LyasesMice, Inbred C57BLPseudomonas InfectionsReactive Oxygen SpeciesSputumStaphylococcal InfectionsStaphylococcus aureusStress, PhysiologicalSuccinatesSuccinic AcidYoung AdultConceptsImmunometabolic responsesS. aureusChronic airway infectionStaphylococcus aureusAirway infectionProminent human pathogenChronic infectionGram-negative pathogensHuman airwaysImmune defenseGlycolytic activityElectrophilic metabolitesInfectionSynthetic enzymesAureusHuman pathogensBiofilm formationMitochondrial stressGlycolysisResponseAirwayPathogensMicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease
Nouws J, Wan F, Finnemore E, Roque W, Kim SJ, Bazan IS, Li CX, Sköld C, Dai Q, Yan X, Chioccioli M, Neumeister V, Britto CJ, Sweasy J, Bindra RS, Wheelock ÅM, Gomez JL, Kaminski N, Lee PJ, Sauler M. MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease. JCI Insight 2021, 6: e134218. PMID: 33290275, PMCID: PMC7934877, DOI: 10.1172/jci.insight.134218.Peer-Reviewed Original ResearchConceptsCellular stress responseStress responseHomology-directed DNA repairDNA damage responseProtein BRCA1Damage responseCellular stressDNA repairProtein BimCOPD lung tissueLung epithelial cellsCellular responsesExpression arraysEpithelial cell apoptosisDNA damageChronic obstructive pulmonary diseaseBRCA1 expressionCell apoptosisApoptosisEpithelial cellsCritical mechanismMicroRNAsRegulatorObstructive pulmonary diseaseIncreases Susceptibility
2020
Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation
Riquelme SA, Liimatta K, Wong Fok Lung T, Fields B, Ahn D, Chen D, Lozano C, Sáenz Y, Uhlemann AC, Kahl BC, Britto CJ, DiMango E, Prince A. Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation. Cell Metabolism 2020, 31: 1091-1106.e6. PMID: 32428444, PMCID: PMC7272298, DOI: 10.1016/j.cmet.2020.04.017.Peer-Reviewed Original ResearchConceptsHost immune responseImmune responseDownregulation of lipopolysaccharidesIntractable pneumoniaPseudomonas aeruginosaInfected lungsChronic infectionImmune clearanceHuman airwaysImmunostimulatory propertiesMyeloid cellsHigh mortalityAirwayInfectionOpportunistic bacteriaLipopolysaccharideAeruginosaBiofilm formationResponsePneumoniaLungTherapyMortalityClearanceUpregulationMechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens
Sharma L, Feng J, Britto CJ, Dela Cruz CS. Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens. Frontiers In Immunology 2020, 11: 91. PMID: 32117248, PMCID: PMC7027138, DOI: 10.3389/fimmu.2020.00091.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBacterial lung infectionsImmune cellsBacterial clearanceRespiratory bacterial pathogensEpithelial cellsLung infectionSecretion of cytokinesEpithelial host defenseMuco-ciliary clearanceHuge economic burdenRespiratory epithelial cellsLung epithelial surfaceMajor healthcare challengeEpithelial immune mechanismsBacterial pathogensAntimicrobial peptide productionImmune mechanismsImmune protectionMucus productionEconomic burdenPathogen clearanceEpithelial immunityHost defenseClinical researchEpithelial resistance
2019
CFTR-PTEN–dependent mitochondrial metabolic dysfunction promotes Pseudomonas aeruginosa airway infection
Riquelme SA, Lozano C, Moustafa AM, Liimatta K, Tomlinson KL, Britto C, Khanal S, Gill SK, Narechania A, Azcona-Gutiérrez JM, DiMango E, Saénz Y, Planet P, Prince A. CFTR-PTEN–dependent mitochondrial metabolic dysfunction promotes Pseudomonas aeruginosa airway infection. Science Translational Medicine 2019, 11 PMID: 31270271, PMCID: PMC6784538, DOI: 10.1126/scitranslmed.aav4634.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarboxy-LyasesColony Count, MicrobialCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorHCT116 CellsHumansHypoxia-Inducible Factor 1, alpha SubunitImmunityInterleukin-1betaLungMice, Inbred C57BLMiddle AgedMitochondriaOxidantsOxidative StressPseudomonas aeruginosaPseudomonas InfectionsPTEN PhosphohydrolaseReactive Oxygen SpeciesSuccinatesConceptsCystic fibrosis transmembrane conductance regulatorImmune-responsive gene 1Fibrosis transmembrane conductance regulatorEffect of PTENTransmembrane conductance regulatorPlasma membraneChromosome 10Reactive oxygen speciesConductance regulatorTumor suppressorTensin homologGene 1Mitochondrial functionMitochondrial activityAnti-inflammatory host responsesCell proliferationOxygen speciesPTENMyeloid cellsCFTR dysfunctionMetabolic defectsHost responseActivity contributesHomologComplexes
2018
BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation
Britto CJ, Niu N, Khanal S, Huleihel L, Herazo-Maya J, Thompson A, Sauler M, Slade MD, Sharma L, Dela Cruz CS, Kaminski N, Cohn LE. BPIFA1 regulates lung neutrophil recruitment and interferon signaling during acute inflammation. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2018, 316: l321-l333. PMID: 30461288, PMCID: PMC6397348, DOI: 10.1152/ajplung.00056.2018.Peer-Reviewed Original ResearchConceptsLung inflammationAcute inflammationC motif chemokine ligand 10Lung neutrophil recruitmentRegulation of CXCL10Acute lung inflammationBronchoalveolar lavage concentrationsChemokine ligand 10Innate immune responseIFN regulatory factorIntranasal LPSLavage concentrationsLung recruitmentNeutrophil recruitmentWT miceImmune effectsLung diseasePMN recruitmentInflammatory responseLPS treatmentLung tissueInflammatory signalsImmune responseImmunomodulatory propertiesInflammationRegulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae
Sharma L, Amick AK, Vasudevan S, Lee SW, Marion CR, Liu W, Brady V, Losier A, Bermejo SD, Britto CJ, Lee CG, Elias JA, Dela Cruz CS. Regulation and Role of Chitotriosidase during Lung Infection with Klebsiella pneumoniae. The Journal Of Immunology 2018, 201: 615-626. PMID: 29891554, PMCID: PMC6291403, DOI: 10.4049/jimmunol.1701782.Peer-Reviewed Original ResearchConceptsLung infectionMouse modelRole of chitotriosidaseBronchoalveolar lavage fluidNumber of neutrophilsSimilar inflammatory responseRole of CHIT1Antibiotic therapyImproved survivalInflammatory changesLavage fluidInflammatory responseNeutrophil proteasesBacterial disseminationTrue chitinasesInfectionBeneficial effectsDetrimental roleAkt pathwayKlebsiella pneumoniaeAkt inhibitorCHIT1Chitinase-like proteinsMiceAkt activation
2017
Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages
Di Pietro C, Zhang PX, O’Rourke T, Murray TS, Wang L, Britto CJ, Koff JL, Krause DS, Egan ME, Bruscia EM. Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages. Scientific Reports 2017, 7: 10882. PMID: 28883468, PMCID: PMC5589856, DOI: 10.1038/s41598-017-11012-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletal ProteinsDisease Models, AnimalMacrophage ActivationMacrophagesMicePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPseudomonas aeruginosaPseudomonas InfectionsSignal TransductionToll-Like Receptor 4ConceptsCystic fibrosis transmembrane conductance regulatorPI3K/AktFibrosis transmembrane conductance regulatorTransmembrane conductance regulatorPI3K/Akt signalingConductance regulatorAnti-bacterial immune responseAkt signalingAltered localizationEzrinCystic fibrosis diseaseMφ activationAktProtein levelsFibrosis diseaseActivationImmune regulationPhagocytosisInductionDirect linkSignalingRegulatorImmune responseMΦMacrophages
2015
Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease
Britto CJ, Cohn L. Bactericidal/Permeability-Increasing Protein Fold–Containing Family Member A1 in Airway Host Protection and Respiratory Disease. American Journal Of Respiratory Cell And Molecular Biology 2015, 52: 525-534. PMID: 25265466, PMCID: PMC4491141, DOI: 10.1165/rcmb.2014-0297rt.BooksConceptsPulmonary diseaseHost protectionChronic obstructive pulmonary diseaseObstructive pulmonary diseaseIdiopathic pulmonary fibrosisMember A1Immune cell functionMultiple lung diseasesBactericidal/permeability-increasing proteinRespiratory malignanciesPulmonary pathogenesisPulmonary fibrosisPermeability-increasing proteinRespiratory secretionsLung diseaseUpper airwayRespiratory tractRespiratory diseaseProximal tracheaImmunomodulatory propertiesBPIFA1Cystic fibrosisDiseasePotential drug targetsEnvironmental exposures
2013
Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity
Britto CJ, Liu Q, Curran DR, Patham B, Dela Cruz CS, Cohn L. Short Palate, Lung, and Nasal Epithelial Clone–1 Is a Tightly Regulated Airway Sensor in Innate and Adaptive Immunity. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 717-724. PMID: 23470624, PMCID: PMC3727874, DOI: 10.1165/rcmb.2012-0072oc.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsCell Line, TumorGene Expression RegulationGlycoproteinsHumansImmunity, InnateImmunohistochemistryInflammationInfluenza A virusInterferon-gammaLipopolysaccharidesLungMiceMice, Inbred C57BLPhosphoproteinsPneumonia, BacterialPseudomonas aeruginosaRespiratory MucosaRespiratory Tract InfectionsStreptococcus pneumoniaeConceptsNasal epithelial clone 1Lower respiratory tractRespiratory tractAirway inflammationShort palateTh2-induced airway inflammationHost defenseAllergic airway inflammationCommon respiratory pathogensAirway epithelial cellsModel of pneumoniaAirway surface liquidPathogen-associated molecular patternsGreatest environmental exposureClone 1Mucociliary clearanceRespiratory pathogensAirway sensorsRespiratory epitheliumAdaptive immunitySPLUNC1IFN-γ actBasal conditionsMRNA expressionMolecular patterns