2022
Inflammasome activation in infected macrophages drives COVID-19 pathology
Sefik E, Qu R, Junqueira C, Kaffe E, Mirza H, Zhao J, Brewer JR, Han A, Steach HR, Israelow B, Blackburn HN, Velazquez SE, Chen YG, Halene S, Iwasaki A, Meffre E, Nussenzweig M, Lieberman J, Wilen CB, Kluger Y, Flavell RA. Inflammasome activation in infected macrophages drives COVID-19 pathology. Nature 2022, 606: 585-593. PMID: 35483404, PMCID: PMC9288243, DOI: 10.1038/s41586-022-04802-1.Peer-Reviewed Original ResearchConceptsInflammasome activationLung inflammationInflammatory responseInfected macrophagesSARS-CoV-2 infectionHuman macrophagesChronic lung pathologyPersistent lung inflammationSevere COVID-19Immune inflammatory responseInflammatory cytokine productionHumanized mouse modelNLRP3 inflammasome pathwayCOVID-19 pathologyCOVID-19SARS-CoV-2Productive viral cycleHyperinflammatory stateChronic stageIL-18Cytokine productionInflammatory cytokinesLung pathologyInflammasome pathwayInterleukin-1
2020
Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity
Jarret A, Jackson R, Duizer C, Healy ME, Zhao J, Rone JM, Bielecki P, Sefik E, Roulis M, Rice T, Sivanathan KN, Zhou T, Solis AG, Honcharova-Biletska H, Vélez K, Hartner S, Low JS, Qu R, de Zoete MR, Palm NW, Ring AM, Weber A, Moor AE, Kluger Y, Nowarski R, Flavell RA. Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity. Cell 2020, 180: 50-63.e12. PMID: 31923399, PMCID: PMC7339937, DOI: 10.1016/j.cell.2019.12.016.Peer-Reviewed Original ResearchConceptsEnteric nervous systemSingle-cell sequencingMucosal barrier immunitySingle-molecule fluorescenceIL-18Non-redundant roleSitu mRNA hybridization studiesEpithelial cellsUnbiased RNA sequencingRNA sequencingProtein responseBarrier immunityNervous systemConfocal microscopyCytokine IL-18Hybridization studiesInvasive bacterial infectionsSalmonella typhimurium infectionSequencingProfound consequencesIntestinal neuronsEnteric neuronsIntestinal immunityMucosal barrierTyphimurium infection