Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 2010 Jan 1;184(1):296-302. doi: 10.4049/jimmunol.0900604. Epub 2009 Nov 30.
The inflammatory response to Pseudomonas aeruginosa is not properly regulated in the lungs of patients with cystic fibrosis (CF). In the lung epithelium of individuals with wild-type CF transmembrane conductance regulator, lipid rafts containing CF transmembrane conductance regulator are rapidly formed in response to P. aeruginosa infection, and this response is closely linked to resistance to infection and disease. We found these rafts also contained high levels of caveolin-1 and thus examined the sensitivity of cav1 knockout (KO) mice to P. aeruginosa challenge in both acute and chronic P. aeruginosa infection models. We found that cav1 KO mice had increased sensitivity to P. aeruginosa infection, as represented by an increased mortality rate, elevated bacterial burdens recovered from lungs and spleens, and elevated inflammatory responses. These findings correlated with the decreased ability of cav1-deficient neutrophils to phagocytose P. aeruginosa. In addition, P. aeruginosa colonized cav1 KO mice much better compared with the wild-type controls in a model of chronic infection, indicting an important contribution of Cav-1 to innate host immunity to P. aeruginosa infection in the setting of both acute pneumonia and chronic infection typical of CF.
在囊性纤维化（CF）患者的肺部，铜绿假单胞菌的炎症反应不能得到适当的调节。在具有野生型 CF 跨膜电导调节剂的个体的肺上皮中，脂质筏在受到铜绿假单胞菌感染时会迅速形成，这种反应与对感染和疾病的抵抗力密切相关。我们发现这些筏还含有高水平的窖蛋白-1，因此我们在急性和慢性铜绿假单胞菌感染模型中检查了 cav1 敲除（KO）小鼠对铜绿假单胞菌挑战的敏感性。我们发现 cav1 KO 小鼠对铜绿假单胞菌感染的敏感性增加，表现为死亡率增加、从肺部和脾脏中回收的细菌负荷增加以及炎症反应增加。这些发现与 cav1 缺陷中性粒细胞吞噬铜绿假单胞菌的能力降低有关。此外，与野生型对照相比，在慢性感染模型中，铜绿假单胞菌在 cav1 KO 小鼠中定植得更好，表明 Cav-1 对急性肺炎和 CF 典型的慢性感染中铜绿假单胞菌感染的固有宿主免疫有重要贡献。
