Waldstein Kody A, Issimov Arman, Ganama Maria, Jinge Valerie, Tilley Stephen, Hua Xiaoyang
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA.
Department of Otorhinolaryngology-Head and Neck Surgery, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Int Forum Allergy Rhinol. 2024 Dec;14(12):1857-1868. doi: 10.1002/alr.23426. Epub 2024 Aug 7.
Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.
In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.
Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced T2 and T17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted infection with RSV recruited Ly6C+ inflammatory monocytes (IMs) into the lungs of mice with and without HDM-induced asthma. The expression of monocyte chemokines, including CCL2 and CCL7, also increased. Interestingly, nasal virus infection-induced AHR was abolished in mice depleted of IMs and in CCR2 mice, indicating that the recruited IMs play a key role in nasal virus infection-induced asthma exacerbations in mice. Lastly, we observed that recruitment of Ly6C+ IMs following URVI was abolished in mice lacking B cells and that nasal-restricted infection with RSV increased numbers of CCL2+CCL7+ B cells in the lungs of mice as compared to controls.
Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.
上呼吸道病毒感染（URVIs）是80%哮喘加重发作的病因。然而，其潜在机制仍知之甚少。
在本研究中，我们使用URVI小鼠模型，研究URVI对哮喘表型的影响及其潜在机制。
此前，我们报道过呼吸道合胞病毒（RSV）鼻腔局限性感染仅产生轻度鼻-鼻窦炎和黏液分泌，不会引起直接的肺部感染。然而，这种鼻腔局限性感染显著增强了屋尘螨（HDM）诱导的哮喘小鼠肺部的2型和17型炎症反应，并增加了气道高反应性（AHR）。此外，RSV鼻腔局限性感染使有或无HDM诱导哮喘的小鼠肺部募集了Ly6C⁺炎性单核细胞（IMs）。包括CCL2和CCL7在内的单核细胞趋化因子的表达也增加。有趣的是，在缺乏IMs的小鼠和CCR2小鼠中，鼻病毒感染诱导的AHR消失，这表明募集的IMs在鼻病毒感染诱导的小鼠哮喘加重中起关键作用。最后，我们观察到在缺乏B细胞的小鼠中，URVI后Ly6C⁺IMs的募集消失，并且与对照组相比，RSV鼻腔局限性感染使小鼠肺部CCL₂⁺CCL₇⁺B细胞数量增加。
综上所述，我们的数据表明，URVI通过B细胞-单核细胞调节轴增强过敏性炎症反应和AHR。
