Pseudomonas aeruginosa is an opportunistic pathogen, which can cause lethal lung infections in humans with altered host defenses. Airway epithelial cells are critical in host pulmonary defense against pathogens and their activities need to be finely tuned to maintain pulmonary homeostasis. Gap junction channels, formed by connexin (Cx) proteins, allow direct cell-to-cell communication between adjacent cells. The aim of the thesis project was to investigate whether gap junctions provide a mechanism to coordinate and regulate the airway epithelial innate response. Altogether the results presented in this manuscript indicate that regulation of Cx43 expression and function may represent a defense mechanism of the airway epithelium against P. aeruginosa infection, in order to induce mucus hydration and mediate apoptosis. These innate mechanisms promote pathogens elimination and the maintenance of airway homeostasis. However, P. aeruginosa can affect the integrity of epithelial gap junctions in non-polarized repairing cells through the quorum sensing molecule C12.