These data further link the CFTR defect to autophagy deficiency and demonstrate the potential of the PI3K/Akt/mTOR pathway for therapeutic targeting in CF.
Because PI3K/AKT signaling is critical for immune regulation, Ezrin-deficient MΦs are hyperinflammatory and have impaired Pseudomonas aeruginosa phagocytosis, phenocopying CF MΦs.
We found that Ptenl<sup>-/-</sup> mice, which lack the NH<sub>2</sub>-amino terminal splice variant of PTEN, were unable to eradicate Pseudomonas aeruginosa from the airways and could not generate sufficient anti-inflammatory PI3K activity, similar to what is observed in CF.