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 stressGlycolysisResponseAirwayPathogens
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 ResearchMeSH KeywordsAnimalsBiofilmsHumansMiceMice, Inbred C57BLMice, KnockoutPseudomonas aeruginosaSuccinatesConceptsHost immune responseImmune responseDownregulation of lipopolysaccharidesIntractable pneumoniaPseudomonas aeruginosaInfected lungsChronic infectionImmune clearanceHuman airwaysImmunostimulatory propertiesMyeloid cellsHigh mortalityAirwayInfectionOpportunistic bacteriaLipopolysaccharideAeruginosaBiofilm formationResponsePneumoniaLungTherapyMortalityClearanceUpregulation
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 ResearchMeSH KeywordsAcute DiseaseAnimalsGlycoproteinsInflammationLipopolysaccharidesLungMice, Inbred C57BLNeutrophil InfiltrationPhosphoproteinsConceptsLung 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 propertiesInflammation
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