Compared to other RV species, RV-C has been associated with more severe respiratory illness and is more likely to occur in children with a history of asthma or who develop asthma. We therefore inoculated 6-day-old mice with sham, RV-A1B, or RV-C15. Inflammasome priming and activation were assessed, and selected mice treated with recombinant IL-1β. Compared to RV-A1B infection, RV-C15 infection induced an exaggerated asthma phenotype, with increased mRNA expression of Il5, Il13, Il25, Il33, Muc5ac, Muc5b, and Clca1; increased lung lineage-negative CD25+CD127+ST2+ ILC2s; increased mucous metaplasia; and increased airway responsiveness. Lung vRNA, induction of pro-inflammatory type 1 cytokines, and inflammasome priming (pro-IL-1β and NLRP3) were not different between the two viruses. However, inflammasome activation (mature IL-1β and caspase-1 p12) was reduced in RV-C15-infected mice compared to RV-A1B-infected mice. A similar deficiency was found in cultured macrophages. Finally, IL-1β treatment decreased RV-C-induced type 2 cytokine and mucus-related gene expression, ILC2s, mucous metaplasia, and airway responsiveness but not lung vRNA level. We conclude that RV-C induces an enhanced asthma phenotype in immature mice. Compared to RV-A, RV-C-induced macrophage inflammasome activation and IL-1β are deficient, permitting exaggerated type 2 inflammation and mucous metaplasia.

与其他 RV 物种相比，RV-C 与更严重的呼吸道疾病有关，并且更有可能发生在有哮喘病史或发展为哮喘的儿童中。因此，我们给 6 天大的小鼠接种了假疫苗、RV-A1B 或 RV-C15。评估了炎性体的启动和激活，并选择了用重组 IL-1β 治疗的小鼠。与 RV-A1B 感染相比，RV-C15 感染诱发了更严重的哮喘表型，Il5、Il13、Il25、Il33、Muc5ac、Muc5b和Clca1的 mRNA 表达增加; 肺谱系阴性 CD25+CD127+ST2+ ILC2 增加；粘液化生增加; 并增加气道反应性。肺部 vRNA、促炎 1 型细胞因子的诱导和炎性体启动（pro-IL-1β 和 NLRP3）在两种病毒之间没有差异。然而，与感染 RV-A1B 的小鼠相比，感染 RV-C15 的小鼠的炎性体激活（成熟的 IL-1β 和 caspase-1 p12）减少。在培养的巨噬细胞中发现了类似的缺陷。最后，IL-1β 治疗降低了 RV-C 诱导的 2 型细胞因子和粘液相关基因表达、ILC2、粘液化生和气道反应性，但不降低肺 vRNA 水平。我们得出结论，RV-C 在未成熟小鼠中诱导增强的哮喘表型。与 RV-A 相比，RV-C 诱导的巨噬细胞炎性体激活和 IL-1β 存在缺陷，