Department of Physiology & Pharmacology, Cumming School of Medicine, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Front Cell Infect Microbiol. 2020 Mar 13;10:103. doi: 10.3389/fcimb.2020.00103. eCollection 2020.
Human rhinovirus (HRV) is a major trigger of acute exacerbations of both asthma and chronic obstructive pulmonary disease. The airway epithelium is the primary site of HRV infection, and responds by releasing proinflammatory and antimicrobial cytokines. Epithelial cells release IL-17C in response to exposure to bacterial, viral, and fungal pathogens. We previously demonstrated a role for HRV in IL-17C production from undifferentiated epithelial cells, and showed that IL-17C could play a role in neutrophil recruitment. To extend these observations, highly differentiated human bronchial epithelial cells (HBE) were infected apically with HRV to assess the effect of dose, time, viral replication, and strain on the IL-17C response. Cellular lysates, and basolateral and apical secretions were analyzed for IL-17C and CXCL1 protein release following HRV or IL-17C stimulation. Upon HRV infection, IL-17C protein was exclusively released basolaterally in a dose-, time-, and viral replication-dependent manner. Several strains of rhinovirus were capable of inducing IL-17C release. Enriched columnar epithelial cell populations contained significantly higher viral titer, and expressed significantly more IL-17C mRNA than enriched basal cell populations. In addition, the kinetic profile of IL-17C release following HRV treatment closely mimics viral shedding kinetics, further implicating the role of rhinovirus replication in IL-17C production. Basolateral treatment of HBEs with IL-17C resulted in a dose-dependent increase in basolateral CXCL1 production. In summary, replicating rhinovirus drives basolateral IL-17C protein release from both apical and basal epithelial cells, which may then act in an autocrine/paracrine manner to promote basolateral CXCL1 protein release.
人鼻病毒（HRV）是哮喘和慢性阻塞性肺疾病急性加重的主要诱因。气道上皮细胞是 HRV 感染的主要部位，会通过释放促炎和抗微生物细胞因子做出反应。上皮细胞在暴露于细菌、病毒和真菌病原体时会释放白细胞介素 17C。我们之前证明了 HRV 在未分化上皮细胞产生白细胞介素 17C 中的作用，并表明白细胞介素 17C 可以在中性粒细胞募集中发挥作用。为了扩展这些观察结果，我们用 HRV 感染高度分化的人支气管上皮细胞（HBE）的顶端，以评估剂量、时间、病毒复制和株系对白细胞介素 17C 反应的影响。在 HRV 或白细胞介素 17C 刺激后，分析细胞裂解物以及基底外侧和顶端分泌物中白细胞介素 17C 和 CXCL1 蛋白的释放。在 HRV 感染后，白细胞介素 17C 蛋白以剂量、时间和病毒复制依赖的方式仅从基底外侧释放。几种鼻病毒株能够诱导白细胞介素 17C 的释放。富含柱状上皮细胞的群体中病毒滴度显著更高，并且表达的白细胞介素 17C mRNA 也显著高于富含基底细胞的群体。此外，HRV 处理后白细胞介素 17C 释放的动力学谱与病毒脱落的动力学谱非常相似，这进一步表明鼻病毒复制在白细胞介素 17C 产生中的作用。HRV 处理后，基底外侧处理 HBE 会导致基底外侧 CXCL1 产生呈剂量依赖性增加。总之，复制的鼻病毒会从顶端和基底上皮细胞中驱动基底外侧白细胞介素 17C 蛋白的释放，然后可能以自分泌/旁分泌的方式发挥作用，促进基底外侧 CXCL1 蛋白的释放。
