Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea.
Clin Exp Allergy. 2018 Mar;48(3):253-265. doi: 10.1111/cea.13082. Epub 2018 Feb 1.
Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown.
To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment.
Influenza A virus mRNA, viral titres and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection.
Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN-β and IFN-λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titres in IAV-infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV-infected AR mouse.
Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.
由于干扰素（IFN）相关免疫反应受损，过敏性呼吸道疾病与病毒感染易感性增加有关，但过敏性疾病中针对病毒感染增强黏膜免疫的机制在很大程度上尚不清楚。
确定过敏性鼻黏膜中 IFN 的诱导是否受损，并确定 IFN 治疗是否可以控制过敏性鼻黏膜中甲型流感病毒（IAV）的更高负荷。
比较 IAV 感染的正常人鼻上皮（NHNE，N=10）和变应性鼻炎鼻上皮（ARNE，N=10）细胞中的 IAV mRNA、病毒滴度和 IFN 表达。我们使用变应性鼻炎（BALB/c 小鼠，N=10）和健康志愿者（N=72）及变应性鼻炎患者（N=29）的体内模型来评估 IAV 感染后 IFN 的诱导。
ARNE 细胞中的 IAV mRNA 水平和病毒滴度明显高于 NHNE 细胞。NHNE 和 ARNE 细胞在 IAV 感染后 3 天内诱导 IFN-β和 IFN-λs。有趣的是，ARNE 细胞中 IFN-λs mRNA 水平和分泌蛋白的诱导明显较低。AR 患者鼻黏膜中的平均 IFN-λs mRNA 水平也明显较低，我们发现重组 IFN-λ 治疗可减轻 IAV 感染的 ARNE 细胞中的病毒 mRNA 水平和病毒滴度。体内 AR 小鼠在 IAV 感染后病毒载量更高，但 IAV 感染 AR 小鼠鼻黏膜中 IFN-λ 的鼻内接种完全降低了 IAV 蛋白表达和病毒滴度。
过敏性鼻黏膜对 IAV 的更高易感性可能取决于 III 型 IFN 诱导的受损，而 III 型 IFN 是过敏性鼻黏膜中更高病毒载量和控制 IAV 感染的关键机制联系。
