title: NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence.
abstract: Bacterial pneumonia is a major cause of acute lung injury and acute respiratory distress syndrome, characterized by alveolar barrier disruption. NLRP3 is best known for its ability to form inflammasomes and to regulate IL-1β and IL-18 production in myeloid cells. Here we show that NLRP3 protects the integrity of the alveolar barrier in a mouse model of Streptococcus pneumoniae-induced pneumonia, and ex vivo upon treatment of isolated perfused and ventilated lungs with the purified bacterial toxin, pneumolysin. We reveal that the preserving effect of NLRP3 on the lung barrier is independent of inflammasomes, IL-1β and IL-18. NLRP3 improves the integrity of alveolar epithelial cell monolayers by enhancing cellular adherence. Collectively, our study uncovers a novel function of NLRP3 by demonstrating that it protects epithelial barrier function independently of inflammasomes.
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Kostadinova
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Catherine
authors.initials: C
authors.lastname: Chaput
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Birgitt
authors.initials: B
authors.lastname: Gutbier
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Lippmann
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Leif E
authors.initials: LE
authors.lastname: Sander
authors.affiliation: Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15-2TT, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mitchell
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Suttorp
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Witzenrath
authors.affiliation: Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Opitz
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000502:physiology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000472:pathogenicity; D013301:Streptolysins / Q000378:metabolism; D055397:Ventilator-Induced Lung Injury / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae