Excessive lung inflammation and airway epithelium damage are hallmarks of cystic fibrosis (CF) disease. It is unclear whether lung inflammation is related to an intrinsic defect in the immune response or to chronic infection. We aimed to determine whether TLR5-mediated response is defective in the CF airway epithelium. We used a newborn CF pig model to study intrinsic alterations in CF airway epithelium innate immune response. Airway epithelial cells (AECs) were stimulated with flagellin or lipopolysaccharide to determine responses specific for TLR5 and TLR4, respectively. We observed a significant increase in cytokine secretion when CF AECs were stimulated with flagellin compared to wild type (WT) AECs. These results were recapitulated when AECs were treated with an inhibitor of CFTR channel activity. We show that TLR5-signalling is altered in CF lung epithelium at birth. Modulation of TLR5 signalling could contribute to better control the excessive inflammatory response observed in CF lungs.

过度的肺部炎症和气道上皮损伤是囊性纤维化 (CF) 疾病的标志。目前尚不清楚肺部炎症是否与免疫反应的内在缺陷或慢性感染有关。我们旨在确定 TLR5 介导的反应是否在 CF 气道上皮细胞中存在缺陷。我们使用新生 CF 猪模型来研究 CF 气道上皮先天免疫反应的内在改变。用鞭毛蛋白或脂多糖刺激气道上皮细胞 (AEC) 以分别确定对 TLR5 和 TLR4 的特异性反应。与野生型 (WT) AEC 相比，当用鞭毛蛋白刺激 CF AEC 时，我们观察到细胞因子分泌显着增加。当用 CFTR 通道活性抑制剂处理 AEC 时，这些结果得到了概括。我们表明，出生时 CF 肺上皮细胞中的 TLR5 信号传导发生了改变。TLR5 信号的调节有助于更好地控制在 CF 肺中观察到的过度炎症反应。