Th1和Th17细胞功能失调在铜绿假单胞菌慢性肺部感染中的致病作用  

The role of Th1/Th17 cells in the pathogenesis of chronic Pseudomonas aeruginosa lung infection

作　　者：丁凤鸣[1] 朱松雷[1] 沈策[1] 

机构地区：[1]上海交通大学附属第六人民医院呼吸科,200233

出　　处：《免疫学杂志》2012年第6期510-514,518,共6页Immunological Journal

摘　　要：目的探讨CD4+T辅助细胞在铜绿假单胞菌(Pseudomonas aeruginosa,PA)慢性肺部感染小鼠体内的功能状态,及其在肺部免疫性病理损伤过程中所起的作用。方法 72只雌性Balb/c小鼠随机气道接种无菌琼脂糖珠(对照组)、低浓度PA琼脂糖珠(低浓度PA组)和高浓度PA琼脂糖珠(高浓度PA组)。在术后第1、3、5和7天处死小鼠,并行支气管肺泡灌洗液白细胞计数、细菌培养、肺组织病理检查、细胞因子分析、CD4+T辅助细胞转录因子real-time PCR检测。结果高浓度PA组小鼠肺部呈现PA慢性感染表现。术后第3天起,高浓度PA组小鼠灌洗液白细胞总数、肺组织病理损伤程度、肺部Th1/Th17细胞因子和转录因子表达水平均显著高于低浓度PA组和对照组。高浓度PA组和低浓度PA组小鼠的Th2免疫反应在病程第5天和第7天无显著差异。结论在PA慢性感染早期,肺组织存在Th1和Th17细胞功能持续亢进,导致肺组织发生免疫性病理损伤,加重了肺部感染病情。[Abstract] This study aimed to investigate the immunopathological role of CD4^＋ T-helper cell subsets in chronic Pseudomonas aeruginosa （PA） lung infection. Total of 72 female Balb/c mice were randomly inoculated with sterileagarose beads （control group）, low concentration of PA-laden agarose beads （low-concentration PA group） and high concentration of PA-laden agarose beads （high-concentration PA group）. These mice were sacrificed at day 1, 3, 5,and 7. Then bronchoalveolar lavage fluid （BALF） cell counts, bacterial quantification and lung tissue histology were performed. Thl/Fh2/-Fhl7 cytokine levels in BALF were measured, and mRNA levels of transcription factors for Thl/ Th2/Thl7 subsets in lung tissues were determined. We found that mice in high-concentration PA group developedchronic PA lung infection. Compared with low-concentration PA group and control group, mice in high-concentration PA group displayed higher BALF cell numbers, more severe lung tissue injury, and a significant increase in Thl/Thl7 cytokines and transcription factors from day 3. There was no significant difference in Th2 response between high-concentration PA group and low-concentration PA group on day 5 and 7. Our results indicated that enhanced Thl/Thl7 responses in mice with chronic PA lung infection could cause immunopathological damages in the lung tissues, and thus deteriorate the disease.

关 键 词：T辅助细胞 铜绿假单胞菌 慢性肺部感染 免疫病理损伤 

分 类 号：R563.1[医药卫生—呼吸系统]