Department of Medical Laboratory, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, PR China.
Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang, 110122, PR China.
Immunotherapy. 2018 Sep;10(12):1065-1076. doi: 10.2217/imt-2018-0059. Epub 2018 Jul 20.
How respiratory syncytial virus (RSV) influences the development of ovalbumin (OVA)-induced asthma remains elusive. As potent T helper (Th)2 cytokine producers, group 2 innate lymphoid cells (ILC2s) are known to serve important functions in the pathogenesis of allergic inflammation. However, how RSV infection affects innate immunity, especially with regard to the function of ILC2s in OVA-induced allergic airway inflammation, is largely unknown.
MATERIALS & METHODS: RSV was used to infect adult BALB/c mice intranasally prior to sensitization and subsequent challenge with OVA. ILC2 frequencies and Th2 cytokine production by ILC2s were assessed by flow cytometry. Cytokine levels were detected both by real-time PCR and ELISA.
Previous infection with RSV attenuated airway inflammation and decreased Th2 cytokine production in mice sensitized and challenged with OVA. Furthermore, previous infection with RSV inhibited the influx of ILC2s into the lung, and constrained their Th2 cytokine production. Adoptive transfer of ILC2s increased asthma-associated airway inflammation in mice previously infected with RSV. These results indicate that previous infection with RSV prevents OVA-induced asthma development via inhibition of ILC2s. Previous infection with RSV attenuated IL-33 production in lung tissue and reduced relative ST2L expression in lung ILC2s, meaning that previous infection with RSV may alter ILC2 function via the IL-33/ST2 signaling pathway.
These results demonstrate that previous infection with RSV attenuates OVA-induced airway inflammation by inhibiting the recruitment and Th2 cytokine production of ILC2s via the IL-33/ST2 pathway.
呼吸道合胞病毒（RSV）如何影响卵清蛋白（OVA）诱导的哮喘的发展仍不清楚。作为强有力的辅助性 T 细胞（Th）2 细胞因子产生者，2 组固有淋巴细胞（ILC2）已知在过敏炎症的发病机制中发挥重要作用。然而，RSV 感染如何影响先天免疫，特别是 ILC2 在 OVA 诱导的过敏性气道炎症中的功能，在很大程度上仍是未知的。
RSV 用于感染成年 BALB/c 小鼠的鼻腔内，然后用 OVA 进行致敏和随后的激发。通过流式细胞术评估 ILC2 频率和 ILC2 产生的 Th2 细胞因子。通过实时 PCR 和 ELISA 检测细胞因子水平。
先前感染 RSV 可减轻 OVA 致敏和激发的小鼠气道炎症和 Th2 细胞因子的产生。此外，RSV 先前的感染抑制了 ILC2 向肺部的流入，并限制了它们的 Th2 细胞因子的产生。先前感染 RSV 的 ILC2 细胞的过继转移增加了与哮喘相关的气道炎症。这些结果表明，RSV 的先前感染通过抑制 ILC2 来预防 OVA 诱导的哮喘发展。RSV 的先前感染减少了肺组织中的 IL-33 产生，并降低了肺 ILC2 中的相对 ST2L 表达，这意味着 RSV 的先前感染可能通过 IL-33/ST2 信号通路改变 ILC2 的功能。
这些结果表明，RSV 的先前感染通过 IL-33/ST2 通路抑制 ILC2 的募集和 Th2 细胞因子的产生，从而减轻 OVA 诱导的气道炎症。
