Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA.
Infect Immun. 2010 Nov;78(11):4542-50. doi: 10.1128/IAI.00302-10. Epub 2010 Aug 23.
Cystic fibrosis (CF) is a genetic disease caused by recessive mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is associated with prevalent and chronic Pseudomonas aeruginosa lung infections. Despite numerous studies that have sought to elucidate the role of CFTR in the innate immune response, the links between CFTR, innate immunity, and P. aeruginosa infection remain unclear. The present work highlights the zebrafish as a powerful model organism for human infectious disease, particularly infection by P. aeruginosa. Zebrafish embryos with reduced expression of the cftr gene (Cftr morphants) exhibited reduced respiratory burst response and directed neutrophil migration, supporting a connection between cftr and the innate immune response. Cftr morphants were infected with P. aeruginosa or other bacterial species that are commonly associated with infections in CF patients, including Burkholderia cenocepacia, Haemophilus influenzae, and Staphylococcus aureus. Intriguingly, the bacterial burden of P. aeruginosa was found to be significantly higher in zebrafish Cftr morphants than in controls, but this phenomenon was not observed with the other bacterial species. Bacterial burden in Cftr morphants infected with a P. aeruginosa ΔLasR mutant, a quorum sensing-deficient strain, was comparable to that in control fish, indicating that the regulation of virulence factors through LasR is required for enhancement of infection in the absence of Cftr. The zebrafish system provides a multitude of advantages for studying the pathogenesis of P. aeruginosa and for understanding the role that innate immune cells, such as neutrophils, play in the host response to acute bacterial infections commonly associated with cystic fibrosis.
囊性纤维化（CF）是一种由囊性纤维化跨膜电导调节因子（CFTR）基因隐性突变引起的遗传疾病，与普遍存在的慢性铜绿假单胞菌肺部感染有关。尽管有许多研究试图阐明 CFTR 在先天免疫反应中的作用，但 CFTR、先天免疫和铜绿假单胞菌感染之间的联系仍不清楚。本研究强调了斑马鱼作为人类感染性疾病，特别是铜绿假单胞菌感染的强大模式生物。cftr 基因表达减少的斑马鱼胚胎（Cftr 突变体）表现出呼吸爆发反应和定向中性粒细胞迁移减少，支持 cftr 与先天免疫反应之间的联系。Cftr 突变体感染铜绿假单胞菌或其他与 CF 患者感染相关的细菌物种，包括洋葱伯克霍尔德菌、流感嗜血杆菌和金黄色葡萄球菌。有趣的是，与对照组相比，斑马鱼 Cftr 突变体中铜绿假单胞菌的细菌负荷明显更高，但这种现象在其他细菌物种中并未观察到。Cftr 突变体感染铜绿假单胞菌ΔLasR 突变体（一种群体感应缺陷株）的细菌负荷与对照组鱼类相当，表明通过 LasR 调节毒力因子的作用对于在缺乏 Cftr 的情况下增强感染是必需的。斑马鱼系统为研究铜绿假单胞菌的发病机制以及了解先天免疫细胞（如中性粒细胞）在宿主对与囊性纤维化相关的急性细菌感染的反应中所起的作用提供了多种优势。
