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

Sci Rep. 2016 Aug 1;6:30943. doi: 10.1038/srep30943.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Cell Adhesion
  • Cells, Cultured
  • Disease Models, Animal
  • Epithelial Cells / immunology*
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Female
  • Inflammasomes / metabolism*
  • Interleukin-18 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology*
  • Pneumonia, Pneumococcal / immunology
  • Pneumonia, Pneumococcal / microbiology
  • Pneumonia, Pneumococcal / prevention & control*
  • Pulmonary Alveoli / immunology*
  • Pulmonary Alveoli / microbiology
  • Pulmonary Alveoli / pathology
  • Signal Transduction
  • Streptococcus pneumoniae / pathogenicity
  • Streptolysins / metabolism
  • Ventilator-Induced Lung Injury / immunology
  • Ventilator-Induced Lung Injury / microbiology
  • Ventilator-Induced Lung Injury / prevention & control*


  • Bacterial Proteins
  • Inflammasomes
  • Interleukin-18
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Streptolysins
  • plY protein, Streptococcus pneumoniae