ected with P. aeruginosa strain 8821. Animal survival was observed for 7 days. P. aeruginosa did not cause mortality in 12537482 mice treated rapamycin or diluent. We next assessed cytokine production and neutrophil infiltration in the lungs and BALF of rapamycin and diluent treated mice. Consistent with the reported anti-inflammatory roles of rapamycin, treatment of mice with rapamycin showed significantly reduced levels of almost every inflammatory cytokine tested. As a result, neutrophil recruitment into the lungs and BALF of rapamycin treated animals was also impaired. Together these data suggest that in spite of the impaired inflammatory responses observed in 
rapamycin treated animals, the accompanying BIRB796 induction of autophagy was able to enhance bacterial clearance above the levels observed in diluent treated animals, supporting a critical role for autophagy in the clearance of P. aeruginosa bacteria in vivo. Discussion P. aeruginosa infection remains the number one cause of morbidity and mortality among cystic fibrosis patients who almost invariably become chronically infected with the bacteria. Autophagy represents an evolutionarily conserved mechanism for the clearance of intracellular pathogens, and recent reports have shown the pathway to be dysregulated in the lungs of cystic fibrosis patients. In the present study we examined the contribution of autophagy to the clearance of the cystic fibrosis pathogen P. aeruginosa. We found that P. aeruginosa induces autophagy in mast cells, which play an important role as sentinel cells during P. aeruginosa lung infection. Furthermore 8832224 bacteria were observed inside autophagosomes, and pharmacological or genetic manipulation of the pathway modulated clearance of internalized bacteria in vitro. Similarly pharmacological modulation of autophagy also modulated clearance of P. aeruginosa from human epithelial cells. Induction of autophagy using rapamcyin was also able to correct defects in the clearance of intracellular bacteria observed in epithelial cells harboring CFTR DF508 mutations. Finally, pharmacological manipulation of the autophagy pathway effectively regulated bacterial clearance from the lungs of infected mice in vivo. Together these findings suggest that autophagy is induced in mast cells and epithelial cells in response to P. aeruginosa. Pharmacological manipulation of autophagy has considerable therapeutic potential for the treatment of P. aeruginosa lung infection. The emergence of multi-antibiotic resistant strains of P. aeruginosa represents a very real threat to the life expectancy and quality of life in cystic fibrosis patients. One possible contributing factor to the antibiotic resistant nature of P. aeruginosa is the observation that the bacteria has the ability infect host cells, where it can survive for long periods of times within the cytosol, sheltered from cell impermeable antibiotics. Normally, intracellular pathogens are targeted for degradation Autophagy and P. aeruginosa Infection through the autophagy pathway. However, the autophagy pathway has been shown to be impaired in cystic fibrosis patients by mutations in CFTR which lead to dysregulation of the beclin-1 PI3K complex. Given our observations that pharmacological manipulation of the autophagy pathway in vivo effectively regulates the clearance of a strain of P. aeruginosa isolated from a cystic fibrosis patient, and that pharmacological induction of autophagy corrects defects in the clearance of intracellular bacter