Background. The chronic airway infection by Pseudomonas aeruginosa (P. aeruginosa) in Cystic Fibrosis (CF) is a pathological manifestation associated with an excessive inflammatory response. The NOD-like receptors (NLRs) are intracellular pattern-recognition receptors that recognize pathogen-associated molecular patterns activating pro-inflammatory response through the assembly of large caspase-1-activating complex, called inflammasome. Recent data suggest that the mitochondria integrate distinct pro-inflammatory signals and relay this information to a key molecular complex related to inflammation, the inflammasome. It has been demonstrated that mitochondria are the main source of inflammasome-activating radical species and as such may constitute the signal-integrating organelle for inflammasome recruitment and activation in P. aeruginosa-driven inflammation in CF. Moreover, in the previous project we have demonstrated that mislocalized CFTR is associated with an increase in intracellular Ca2+ content and that it favored the mitochondrial Ca2+ uptake, predisposing the organelle to a major stress responsivity.

Hypothesis and objectives. The overall goal of this project is to broaden our knowledge on role of mitochondria to decode and integrate the pro-inflammatory signals generated during P. aeruginosa infection in CF. We have performed experiments aimed at obtaining a deeper insight into the complex mechanism that controls the mitochondrial homeostasis, in particular the Ca2+ signal, and the inflammasome activation induced by pathogen in CF