High-mobility group box-1 protein from CC10+ club cells promotes type 2 response in the later stage of respiratory syncytial virus infection
High-mobility group box-1 protein from CC10+ club cells promotes type 2 response in the later stage of respiratory syncytial virus infection
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CC10俱乐部细胞的高迁移率group box-1蛋白促进呼吸道合胞病毒感染后期的2型反应
DOI：
10.1152/ajplung.00552.2017
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发表时间：
2019-01-01
影响因子：
4.9
通讯作者：
Liu, Enmei
中科院分区：
文献类型：
--
作者：
Chen, Sisi;Yu, Guangyuan;Liu, Enmei
由呼吸道合胞病毒（RSV）感染诱导的2型免疫应答与哮喘的发生有关，但仍不清楚这种应答是如何启动的。在这里，我们报道了高迁移率族蛋白1（HMGB 1）蛋白促进RSV感染后期的2型反应。在小鼠中，我们发现2型细胞因子在后期阶段升高，在给予抗HMGB 1抗体后强烈减少。进一步的研究显示HMGB 1的表达定位于肺中的CC 10（+）俱乐部细胞。在临床上，RSV毛细支气管炎患儿鼻咽吸出物中HMGB 1水平[中位数（四分位距）161.20 ng/ml（68.06-221.30）]显著高于非下呼吸道感染患儿[21.94 ng/ml（12.12-59.82）; P < 0.001]。此外，高水平的HMGB 1与临床严重程度相关。这些结果揭示了病毒感染与哮喘样2型反应之间的联系，这些反应与长期后果有关。
The type 2 immune response, induced by infection of respiratory syncytial virus (RSV), has been linked to asthma development, but it remains unclear how the response is initiated. Here, we reported that the high-mobility group box-1 (HMGB1) protein promotes the type 2 response in the later stage of RSV infection. In mice, we found that type 2 cytokines were elevated in the later stages, which were strongly diminished after administration of anti-HMGB1 antibodies. Further investigation revealed that HMGB1 expression was localized to CC10(+) club cells in the lung. In the clinic, levels of HMGB1 in nasopharyngeal aspirates in hospitalized infants with RSV bronchiolitis [median (interquartile range) 161.20 ng/ml (68.06-221.30)] were significantly higher than those without lower respiratory tract infections [21.94 ng/ml (12.12-59.82); P < 0.001]. Moreover, higher levels of HMGB1 correlated with clinical severity. These results reveal a link between viral infection and the asthma-like type 2 responses that are associated with long-term consequences.