Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that controls chloride current. A number of different CFTR transgenic mouse lines have been developed and subjected to both acute and chronic infection models. However, prior studies showed no substantial differences in bacterial clearance between CF and non-CF mice after single inoculations. Here, using F508del transgenic CF mice, we examined the role of repeated acute Pseudomonas aeruginosa (PA) infection, with the second inoculation 7 days after the first. We found that CF mice were more susceptible to PA infection than non-CF mice following the second inoculation, with non-CF mice showing better neutrophil recruitment and effector functions. We further investigated the characteristics of lung immune cells using single-cell RNA sequencing, finding that non-CF lung neutrophils had more prominent upregulation of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) compared to CF lung neutrophils. Although people with CF are often colonized with bacteria and have high numbers of neutrophils in the airways during chronic infection, these data suggest that CF neutrophils have deficient effector functions in the setting of repeated acute infection.

中文翻译：

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囊性纤维化小鼠鼻内接种后对反复急性铜绿假单胞菌肺炎高度敏感

囊性纤维化 (CF) 是一种由控制氯电流的囊性纤维化跨膜电导调节器 (CFTR) 突变引起的遗传性疾病。已经开发出许多不同的 CFTR 转基因小鼠品系，并对其进行急性和慢性感染模型。然而，先前的研究表明，单次接种后 CF 小鼠和非 CF 小鼠的细菌清除率没有显着差异。在这里，我们使用 F508del 转基因 CF 小鼠，检查了重复急性铜绿假单胞菌(PA) 感染的作用，第二次接种是在第一次接种后 7 天。我们发现，第二次接种后，CF 小鼠比非 CF 小鼠更容易受到 PA 感染，非 CF 小鼠表现出更好的中性粒细胞募集和效应功能。我们利用单细胞RNA测序进一步研究了肺免疫细胞的特征，发现与CF肺中性粒细胞相比，非CF肺中性粒细胞的粘附分子包括细胞间粘附分子-1（ICAM-1）的上调更显着。尽管患有CF的人在慢性感染期间经常被细菌定植并且气道中具有大量中性粒细胞，但这些数据表明CF中性粒细胞在反复急性感染的情况下具有缺陷的效应功能。