Respiratory Syncytial Virus Infection Disrupts Airway Epithelial Barriers via IL‐33/ST2/MyD88 Signaling Axis

作者：Qing Miao, Rui Yu, Fanyu Shi, Kaixin Li, Xinqian Du, Yi Gao, Li Y, Ye Cui, Yan Chen, Jie Liu, Zhe Lv, Jing Yuan, Christopher J. Corrigan, Sun Ying, Wei Wang · 发表于：Journal of Medical Virology · 年份：2025 · DOI：10.1002/jmv.70432 · 被引用次数：9 · 研究领域：IL-33, ST2, and ILC Pathways、Respiratory viral infections research、Neonatal Respiratory Health Research

ABSTRACT Respiratory syncytial virus (RSV) infection has been associated with disruption of the airway epithelial barrier, potentially increasing the risk of asthma development. However, whether and how RSV and RSV‐induced IL‐33 contribute to this process are still unclear. In vivo, 7‐day‐old C57BL/6 mice were infected perinasally with RSV, then viral replication, lung inflammation and barrier integrity were evaluated at various time points postinfection. In vitro, human epithelial cells were infected with RSV in the presence or absence of IL‐33, and the expression and localization of apical junction complex proteins (AJC) were assessed by western blot analysis and immunofluorescence staining. The involvement of components of the IL‐33/ST2/MyD88 axis was further verified through blockade of endogenous IL‐33 signaling and pharmacological inhibition of MyD88. Exposure to RSV infection resulted in impairment of the airway epithelial barrier, as indicated by reduced expression of tight junction proteins (ZO‐1, Occludin) and adherents junction protein (E‐cadherin) in the lung tissues. These effects on epithelial barrier disruption were significantly attenuated in St2 ‐/‐ mice compared with wild‐type controls. In vitro, the RSV‐induced epithelial barrier disruption was exacerbated by topical application of exogenous IL‐33, partially through activation of MyD88‐mediated NF‐κB signaling. Notably, knockdown of St2 by siRNA transfection or pharmacological inhibition of MyD88 partially ...