Excessive inflammation by phagocytes during Aspergillus fumigatus infection is thought to promote lung function decline in CF patients. CFTR modulators have been shown to reduce A. fumigatus colonization in vivo, however, their antifungal and anti-inflammatory mechanisms are unclear. Other treatments including azithromycin and acebilustat may dampen Aspergillus-induced inflammation due to their immunomodulatory properties. Therefore, we set out in this study to determine the effects of current CF therapies on ROS production and fungal killing, either direct or indirect by enhancing antifungal immune mechanisms in peripheral blood immune cells from CF patients upon A. fumigatus infection. Isolated peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) from CF patients and healthy volunteers were challenged with A. fumigatus following pre-treatment with CFTR modulators, azithromycin or acebilustat. Ivacaftor/lumacaftor treated CF and control subject PMNs resulted in a significant reduction (p < 0.05) in Aspergillus-induced ROS. For CF PBMC, Aspergillus-induced ROS was significantly reduced when pre-treated with ivacaftor alone (p < 0.01) or in combination with lumacaftor (p < 0.01), with a comparable significant reduction in control subject PBMC (p < 0.05). Azithromycin and acebilustat had no effect on ROS production by CF or control subject phagocytes. None of the treatments showed an indirect or direct antifungal activity. In summary, CFTR modulators have potential for additional immunomodulatory benefits to prevent or treat Aspergillus-induced inflammation in CF. The comparable effects of CFTR modulators observed in phagocytes from control subjects questions their exact mechanism of action.

吞噬细胞过度发炎烟曲霉感染被认为会促进 CF 患者的肺功能下降。CFTR 调制器已被证明可以减少烟曲霉殖民化体内然而，它们的抗真菌和抗炎机制尚不清楚。其他治疗方法，包括阿奇霉素和 acebilustat 可能会抑制曲霉属-由于它们的免疫调节特性而引起的炎症。因此，我们在本研究中着手确定当前 CF 疗法对 ROS 产生和真菌杀伤的影响，直接或间接通过增强 CF 患者外周血免疫细胞的抗真菌免疫机制烟曲霉感染。来自 CF 患者和健康志愿者的分离的外周血单核细胞 (PBMC) 和多形核细胞 (PMN)烟曲霉在用 CFTR 调节剂、阿奇霉素或阿司匹司他进行预处理后。Ivacaftor/lumacaftor 治疗的 CF 和对照受试者 PMN 导致显着减少（p< 0.05) 在曲霉属-诱导的 ROS。对于 CF PBMC，曲霉属单独用ivacaftor预处理时诱导的活性氧显着降低（p< 0.01) 或与 lumacaftor (p< 0.01），对照组 PBMC 显着降低（p< 0.05)。阿奇霉素和阿奇霉素对 CF 或对照受试者吞噬细胞的 ROS 产生没有影响。没有一种处理显示出间接或直接的抗真菌活性。总之，CFTR 调节剂具有预防或治疗额外免疫调节益处的潜力曲霉属- CF中诱导的炎症。在对照受试者的吞噬细胞中观察到的 CFTR 调节剂的类似作用质疑其确切的作用机制。