白介素-17在铜绿假单胞菌肺部感染防御机制中的作用

Interleukin-17 and host defense against Pseudomonas aeruginosa lung infection

目的以小鼠铜绿假单胞菌急性肺部感染为研究对象,探讨白介素-17(IL-17)对铜绿假单胞菌肺部感染的防御机制,为IL-17临床免疫治疗铜绿假单胞菌肺部感染提供理论和实践基础。方法检测小鼠急性铜绿假单胞菌肺部感染IL-17及其下游因子[IL-1β、巨噬细胞炎性蛋白-2(MIP-2)、粒细胞集落刺激因子(G-CSF)]的表达水平,经气道滴入表达IL-17的正义质粒48 h后再感染铜绿假单胞菌,观察铜绿假单胞菌肺部感染小鼠6 h后的细菌清除率、IL-17的下游因子的表达水平,并观察小鼠的死亡率。结果①小鼠铜绿假单胞菌急性肺部感染IL-17及其下游因子IL-1β,MIP-2,G-CSF水平显著增高。②通过气道滴注表达IL-17的正义质粒后IL-17及其下游因子IL-1β、MIP-2、G-CSF水平显著增高,而且中性粒细胞计数也显著增加。③在铜绿假单胞菌急性肺部感染前预先经气管注入表达IL-17的正义质粒使IL-17高表达,导致局部产生IL-1β、MIP-2、G-CSF,细菌的清除率及小鼠生存率也显著提高。结论 IL-17在铜绿假单胞菌肺部感染的局部免疫反应中起一定作用。其机制可能是通过增加早期中性粒细胞募集到感染部位来实现的。

Objective This study aimed to determine whether IL-17 plays an important role in host defense against pulmonary P. aeruginosa infection and whether genetic up regulation of IL 17 could ameliorate acute P. aeruginosa lung infection in mice. Methods The study was conducted with a previously described murine model of acute P. aeruginosa lung infection, lnflamma tory cells in BALF and the levels of cytokines （IL-17, IL- 1β, MIP 2, and G-CSF） were measured. The plasmid encoding rail 17 was instilled via airway to lungs in vivo 48 h before challenging with P. aeruginosa. The bacterial loads, levels of cyto kines/chemokines （IL-1β, MIP 2, and G-CSF） and animal survival rate were measured 6 hours post infection. Results II.-17 production was significantly increased in the lungs after challenging with P. aeruginosa. Administration of the plasmid enco- ding mIL-17 to the lungs of normal mice significantly increased local release of IL-113, MIP-2 and G-CSF, which resulted in re- cruitment of neutrophils to lungs. On the basis of these data, overexpression of IL-17 in the pulmonary compartment using the plasmid resulted in local induction of tumor IL-I^I, MIP-2, G-CSF, significantly higher bacterial clearance and animal survival after challenging with P. aeruginosa. Conclusions Our findings indicate that IL-17 may have a role in local immune response in the context of lung infection, which may be resulted from the recruitment of neutrophils to the site of pulmonary infection.