IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps
IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps
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IFN-lambda 1 增强健康鼻粘膜中金黄色葡萄球菌的清除率，但不增强鼻息肉中的金黄色葡萄球菌清除率
DOI：
10.1016/j.jaci.2018.09.041
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发表时间：
2019-04-01
影响因子：
14.2
通讯作者：
Bachert, Claus
中科院分区：
文献类型：
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作者：
Lan, Feng;Zhong, Hua;Bachert, Claus
背景资料：慢性鼻窦炎伴鼻息肉（CRSwNP）的特征是TH 2-偏斜炎症和金黄色葡萄球菌定植增加。IFN-λ 1因其抗病毒活性而闻名，但关于其抗菌作用的信息很少。目的：我们试图确定健康受试者和CRSwNP患者暴露于金黄色葡萄球菌时鼻粘膜组织中IFN-λ 1的表达和释放，并评估其在抗菌防御机制中的潜在作用。将来自健康受试者和CRSwNP患者的鼻组织暴露于金黄色葡萄球菌，并且我们评估IFN-λ 1、MUC 5AC和MUC 5 B的表达。通过免疫荧光染色评估与或不与IFN-λ 1孵育的THP 1衍生的巨噬细胞对金黄色葡萄球菌的摄取和杀伤以及溶酶体相关膜蛋白1和细胞内反应性氧化酶底物（ROS）、IFN-λ 1受体IL-28受体（IL-28 R）和Janus激酶/信号转导子和转录激活子（STAT）1途径的表达。金黄色葡萄球菌感染增加了CRSwNP患者组织中IFN-Lambda 1的表达。IFN-λ 1（10 ng/mL）显著降低健康对照组织中的金黄色葡萄球菌集落形成单位的数量，但在来自CRSwNP患者的组织中没有，并且在金黄色葡萄球菌感染的对照组织中上调MUC 5AC和MUC 5 B表达。IFN-λ 1刺激增加了THP 1衍生的巨噬细胞中金黄色葡萄球菌的细胞内杀伤，并显著增加了与金黄色葡萄球菌孵育的巨噬细胞中溶酶体相关膜蛋白1、IL-28 R、ROS和STAT信号传导。结论：IFN-λ 1通过IL-28 R-ROS-Janus激酶-STAT信号通路促进健康鼻粘膜金黄色葡萄球菌的清除，增强巨噬细胞的抗菌功能。
Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by TH2-skewed inflammation and increased colonization by Staphylococcus aureus. IFN-lambda 1 is known for its antiviral activity, but there is little information on its antibacterial role.Objective: We sought to determine the expression and release of IFN-lambda 1 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.Methods: Nasal tissue from healthy subjects and patients with CRSwNP was exposed to S aureus, and we assessed expression of IFN-lambda 1, MUC5AC, and MUC5B. THP1-derived macrophages incubated with or without IFN-lambda 1 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-lambda 1 receptor IL-28 receptor (IL-28R), and the Janus kinase/signal transducer and activator of transcription (STAT) 1 pathway by means of immunofluorescence staining.Results: S aureus infection increased IFN-lambda 1 expression in tissue from patients with CRSwNP. IFN-lambda 1 (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-lambda 1 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.Conclusions: IFN-lambda 1 favors clearance of S aureus in healthy nasal mucosa and enhances antibacterial function of macrophages through IFN-lambda 1-IL-28R-ROS-Janus kinase-STAT signaling pathways.