Damlund Dina Silke Malling, Christophersen Lars, Jensen Peter Østrup, Alhede Morten, Høiby Niels, Moser Claus
Department of Clinical Microbiology, Rigshospitalet, Copenhagen, Denmark.
Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
APMIS. 2016 Jun;124(6):500-7. doi: 10.1111/apm.12530. Epub 2016 Mar 24.
The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target.
大多数囊性纤维化（CF）患者会发生慢性铜绿假单胞菌肺部感染，导致死亡率和发病率增加。慢性铜绿假单胞菌肺部感染的特征是细菌在被多形核中性粒细胞（PMN）包围的生物膜中生长。然而，感染并未根除，炎症反应导致肺组织逐渐退化。在CF患者中，以明显的抗体反应为主的Th2型适应性免疫反应与较差的预后相关。树突状细胞（DC）在连接先天免疫系统和适应性免疫反应方面至关重要。一旦被激活，DC会向未分化的T细胞传递一系列信号，诱导其发育，如调节性T细胞的扩增以及Th1、Th2或Th17亚群的极化。在本研究中，我们对通过气管内植入海藻酸盐包埋的铜绿假单胞菌感染的BALB/c小鼠的肺和局部淋巴结中的DC进行了表征。在肺中检测到DC的浓度显著升高的时间早于局部淋巴结。为了评估慢性铜绿假单胞菌肺部感染是否导致DC激活，分析了共刺激分子CD80和CD86。在感染期间，肺和局部淋巴结中的DC均显示CD80和CD86表达显著升高。有趣的是，淋巴结中CD86阳性细胞的百分比显著高于CD80阳性细胞的百分比。此外，分析了脂多糖（LPS）刺激的DC产生的细胞因子，结果显示IL-6、IL-10和IL-12的产生增加。然而，IL-12的产生比IL-6和IL-10更早受到抑制。这些结果支持DC参与了CF中Th1/Th2平衡的偏向，可能是一个潜在的治疗靶点。
