NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence

Elena Kostadinova; Catherine Chaput; Birgitt Gutbier; Juliane Lippmann; Leif E Sander; Timothy J Mitchell; Norbert Suttorp; Martin Witzenrath; Bastian Opitz

doi:10.1038/srep30943

NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence

Elena Kostadinova, Catherine Chaput, Birgitt Gutbier, Juliane Lippmann, Leif E Sander, Timothy J Mitchell, Norbert Suttorp, Martin Witzenrath, Bastian Opitz

Microbiology and Infection

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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.

Original language	English
Article number	30943
Journal	Scientific Reports
Volume	6
Early online date	1 Aug 2016
DOIs	https://doi.org/10.1038/srep30943
Publication status	E-pub ahead of print - 1 Aug 2016

Keywords

Journal Article
Bacterial infection
NOD-like receptors

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Kostadinova_et_al_NLRP3_protects_alveolar_barrier_integrity_Scientific_reports
Scientific Reports 6, Article number: 30943 (2016) doi:10.1038/srep30943
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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.",

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AU - Kostadinova, Elena

AU - Chaput, Catherine

AU - Gutbier, Birgitt

AU - Lippmann, Juliane

AU - Sander, Leif E

AU - Mitchell, Timothy J

AU - Suttorp, Norbert

AU - Witzenrath, Martin

AU - Opitz, Bastian

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - Bacterial infection

KW - NOD-like receptors

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NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence

Abstract

Keywords

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