National Jewish Health, Denver, CO 80206, USA.
Doheny Eye Institute, University of California Los Angeles, Arcadia, CA 91007, USA.
Viruses. 2024 Aug 29;16(9):1384. doi: 10.3390/v16091384.
Allergic asthma is characterized by increased type 2 inflammation, including eosinophils. Subjects with allergic asthma have recurrent symptoms due to their constant exposure to environmental allergens, such as house dust mite (HDM), which can be further exacerbated by respiratory infections like rhinovirus. The immunoproteasome (IP) is a proteolytic machinery that is induced by inflammatory mediators during virus infection, but the role of the IP in airway allergic inflammation during rhinovirus infection remains unknown. Wild-type (WT) and IP knockout (KO) mice were challenged with HDM. At 48 h after the last HDM challenge, mice were infected with rhinovirus 1B (RV-A1B) for 24 h. After HDM and RV-A1B treatment, IP KO (vs. WT) mice had significantly more lung eosinophils and neutrophils, as well as a significantly higher viral load, but less IFN-beta expression, compared to WT mice. A TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) treatment after RV-A1B infection in HDM-challenged IP KO mice significantly increased IFN-beta expression and reduced viral load, with a minimal effect on the number of inflammatory cells. Our data suggest that immunoproteasome is an important mechanism functioning to prevent excessive inflammation and viral infection in allergen-exposed mice, and that Poly I:C could be therapeutically effective in enhancing the antiviral response and lessening the viral burden in lungs with IP deficiency.
过敏性哮喘的特征是 2 型炎症增加，包括嗜酸性粒细胞。过敏性哮喘患者由于持续暴露于环境过敏原（如屋尘螨 [HDM]）而反复出现症状，呼吸道病毒感染（如鼻病毒）可进一步加重这种情况。免疫蛋白酶体（IP）是一种在病毒感染期间由炎症介质诱导的蛋白水解机制，但在鼻病毒感染期间 IP 在气道过敏炎症中的作用尚不清楚。野生型（WT）和 IP 敲除（KO）小鼠接受 HDM 挑战。在最后一次 HDM 挑战后 48 小时，用鼻病毒 1B（RV-A1B）感染小鼠 24 小时。在 HDM 和 RV-A1B 处理后，与 WT 小鼠相比，IP KO（与 WT 相比）小鼠的肺嗜酸性粒细胞和中性粒细胞明显增多，病毒载量明显升高，但 IFN-β表达明显降低。RV-A1B 感染后用 TLR3 激动剂聚肌胞苷酸（Poly I:C）处理 HDM 挑战的 IP KO 小鼠，可显著增加 IFN-β表达并降低病毒载量，对炎症细胞数量的影响最小。我们的数据表明，免疫蛋白酶体是一种重要的机制，可防止过敏原暴露的小鼠发生过度炎症和病毒感染，Poly I:C 可能通过增强抗病毒反应和减轻 IP 缺乏肺部的病毒负担而具有治疗效果。
