Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, North Dakota 58203, USA.
Eur J Immunol. 2012 Jun;42(6):1500-11. doi: 10.1002/eji.201142051.
Caveolin-1 (Cav1) is a structural protein of caveolae. Although Cav1 is associated with certain bacterial infections, it is unknown whether Cav1 is involved in host immunity against Klebsiella pneumoniae, the third most commonly isolated microorganism from bacterial sepsis patients. Here, we showed that cav1 knockout mice succumbed to K. pneumoniae infection with markedly decreased survival rates, increased bacterial burdens, intensified tissue injury, hyperactive proinflammatory cytokines, and systemic bacterial dissemination as compared with WT mice. Knocking down Cav1 by a dominant negative approach in lung epithelial MLE-12 cells resulted in similar outcomes (decreased bacterial clearance and increased proinflammatory cytokine production). Furthermore, we revealed that STAT5 influences the GSK3β-β-catenin-Akt pathway, which contributes to the intensive inflammatory response and rapid infection dissemination seen in Cav1 deficiency. Collectively, our findings indicate that Cav1 may offer resistance to K. pneumoniae infection, by affecting both systemic and local production of proinflammatory cytokines via the actions of STAT5 and the GSK3β-β-catenin-Akt pathway.
窖蛋白-1（Cav1）是质膜窖的结构蛋白。尽管 Cav1 与某些细菌感染有关，但尚不清楚 Cav1 是否参与宿主对肺炎克雷伯菌的免疫反应，肺炎克雷伯菌是细菌性败血症患者中第三常见的分离微生物。在这里，我们表明 Cav1 基因敲除小鼠在感染肺炎克雷伯菌后易受感染，其存活率明显降低，细菌负荷增加，组织损伤加剧，促炎细胞因子过度活跃，全身细菌播散增加，与 WT 小鼠相比。在肺上皮 MLE-12 细胞中通过显性负性方法敲低 Cav1 也会产生类似的结果（细菌清除减少和促炎细胞因子产生增加）。此外，我们揭示了 STAT5 影响 GSK3β-β-catenin-Akt 通路，这有助于 Cav1 缺乏时观察到的强烈炎症反应和快速感染播散。总之，我们的研究结果表明，Cav1 可能通过 STAT5 和 GSK3β-β-catenin-Akt 通路影响全身和局部促炎细胞因子的产生，从而提供对肺炎克雷伯菌感染的抵抗力。
