The tumor suppressor PTEN controls cell proliferation by regulating phosphatidylinositol-3-kinase (PI3K) activity, but the participation of PTEN in host defense against bacterial infection is less well understood. Anti-inflammatory PI3K-Akt signaling is suppressed in patients with cystic fibrosis (CF), a disease characterized by hyper-inflammatory responses to airway infection. We found that Ptenl^−/− mice, which lack the NH₂-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. PTEN and the CF transmembrane conductance regulator (CFTR) interacted directly and this interaction was necessary to position PTEN at the membrane. CF patients under corrector-potentiator therapy, which enhances CFTR transport to the membrane, have increased PTEN amounts. These findings suggest that improved CFTR trafficking could enhance P. aeruginosa clearance from the CF airway by activating PTEN-mediated anti-bacterial responses and might represent a therapeutic strategy.

肿瘤抑制因子 PTEN 通过调节磷脂酰肌醇 3 激酶 (PI3K) 活性来控制细胞增殖，但 PTEN 在宿主防御细菌感染过程中的参与尚不清楚。囊性纤维化 (CF) 患者的抗炎 PI3K-Akt 信号传导受到抑制，囊性纤维化是一种以对气道感染的过度炎症反应为特征的疾病。我们发现，缺乏 PTEN 的 NH ₂ -氨基末端剪接变体的Ptenl ^-/−小鼠无法根除气道中的铜绿假单胞菌，也无法产生足够的抗炎 PI3K 活性，类似于在 CF 中观察到的情况。 PTEN 和 CF 跨膜电导调节因子 (CFTR) 直接相互作用，这种相互作用对于将 PTEN 定位在膜上是必要的。接受校正增效剂治疗（增强 CFTR 向细胞膜转运）的 CF 患者的 PTEN 量增加。这些发现表明，改善 CFTR 运输可以通过激活 PTEN 介导的抗菌反应来增强铜绿假单胞菌从 CF 气道中的清除，并且可能代表一种治疗策略。