Department of Otolaryngology Head and Neck Surgery, Beijing Institute of Otolaryngology, Beijing TongRen Hospital, Capital Medical University, Beijing, China; Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium.
Upper Airways Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium; Otorhinolaryngology Hospital, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
J Allergy Clin Immunol. 2019 Apr;143(4):1416-1425.e4. doi: 10.1016/j.jaci.2018.09.041. Epub 2018 Nov 30.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by T2-skewed inflammation and increased colonization by Staphylococcus aureus. IFN-λ1 is known for its antiviral activity, but there is little information on its antibacterial role.
We sought to determine the expression and release of IFN-λ1 from nasal mucosal tissue of healthy subjects and patients with CRSwNP on exposure to S aureus and assess its potential role in antibacterial defense mechanisms.
Nasal tissue from healthy subjects and patients with CRSwNP was exposed to S aureus, and we assessed expression of IFN-λ1, MUC5AC, and MUC5B. THP1-derived macrophages incubated with or without IFN-λ1 were assessed for uptake and killing of S aureus and expression of lysosomal-associated membrane protein 1 and intracellular reactive oxidase substrate (ROS), the IFN-λ1 receptor IL-28 receptor (IL-28R), and the Janus kinase/signal transducer and activator of transcription (STAT) 1 pathway by means of immunofluorescence staining.
S aureus infection increased IFN-λ1 expression in tissue from patients with CRSwNP. IFN-λ1 (10 ng/mL) significantly decreased the number of S aureus colony-forming units in healthy control tissue but not in tissue from patients with CRSwNP and upregulated MUC5AC and MUC5B expression in control tissue on S aureus infection. IFN-λ1 stimulation increased intracellular killing of S aureus in THP1-derived macrophages and substantially increased lysosomal-associated membrane protein 1, IL-28R, ROS, and STAT signaling in macrophages incubated with S aureus. All of these effects were attenuated by blocking IL-28R and ROS activities.
IFN-λ1 favors clearance of S aureus in healthy nasal mucosa and enhances antibacterial function of macrophages through IFN-λ1-IL-28R-ROS-Janus kinase-STAT signaling pathways.
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）的特征是 T2 偏向炎症和金黄色葡萄球菌定植增加。IFN-λ1 以其抗病毒活性而闻名，但关于其抗菌作用的信息很少。
我们旨在确定健康受试者和 CRSwNP 患者的鼻黏膜组织在暴露于金黄色葡萄球菌后 IFN-λ1 的表达和释放，并评估其在抗菌防御机制中的潜在作用。
将金黄色葡萄球菌暴露于健康受试者和 CRSwNP 患者的鼻组织中，并评估 IFN-λ1、MUC5AC 和 MUC5B 的表达。用或不用 IFN-λ1 孵育 THP1 衍生的巨噬细胞，评估金黄色葡萄球菌的摄取和杀伤以及溶酶体相关膜蛋白 1 和细胞内活性氧化还原底物（ROS）、IFN-λ1 受体 IL-28 受体（IL-28R）和 Janus 激酶/信号转导和转录激活因子（STAT）1 途径的表达通过免疫荧光染色。
金黄色葡萄球菌感染增加了 CRSwNP 患者组织中 IFN-λ1 的表达。IFN-λ1（10ng/mL）显著降低了健康对照组组织中金黄色葡萄球菌的菌落形成单位数量，但对 CRSwNP 患者组织没有影响，并且在金黄色葡萄球菌感染时上调了对照组组织中的 MUC5AC 和 MUC5B 表达。IFN-λ1 刺激增加了 THP1 衍生巨噬细胞中金黄色葡萄球菌的细胞内杀伤，并大大增加了与金黄色葡萄球菌孵育的巨噬细胞中的溶酶体相关膜蛋白 1、IL-28R、ROS 和 STAT 信号。所有这些作用都被阻断 IL-28R 和 ROS 活性所减弱。
IFN-λ1 有利于健康鼻黏膜中金黄色葡萄球菌的清除，并通过 IFN-λ1-IL-28R-ROS-Janus 激酶-STAT 信号通路增强巨噬细胞的抗菌功能。
