C57Bl/6 WT mice were intranasally infected with 107 CFUs of either PAO1, single CF isolates, a mixture of two, or all 17 strains together. (A and B) Mouse survival (five mice per group pooled from n = 2). (C) P. aeruginosa burden in BAL (four to seven mice per group pooled from n = 3). (D to F) Monocytes, neutrophils, and alveolar macrophages found in BAL 24 hours after infection (four to six mice per group pooled from n = 3). CftrΔF508/ΔF508 (gut-corrected) mice were intranasally infected with a mix of 107 CFUs of all 17 CF P. aeruginosa isolates. (G) Succinate in BAL (three to eight mice per group pooled from n = 3). (H to J) Neutrophils, monocytes, and alveolar macrophages found in BAL 48 hours after infection (eight mice per group pooled from n = 3). (K and L) P. aeruginosa burden in BAL and lungs (eight mice per group pooled from n = 3). Ptenl−/− mice were intranasally infected with a mix of 107 CFUs of all 17 CF P. aeruginosa isolates (three to six mice per group pooled from n = 3). The following were analyzed: (M) succinate in BAL; (N) IL-1β in BAL; (O to Q) monocytes, neutrophils, and alveolar macrophages found in BAL 24 hours after infection, (R and S) P. aeruginosa burden in BAL and lungs 24 hours after infection. Data are shown as means ± SEM. (A and B) Kaplan-Meier; (C) two-way ANOVA; (D to G and M to S) one-way ANOVA; (H to L) Student’s t test. ****P < 0.0001; ***P < 0.001; **P < 0.01; *P < 0.05.