Abstract：
BACKGROUND: Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.
METHODS: In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.
RESULTS: 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 TH2 and TH17 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.
CONCLUSIONS: Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.
METHODS: In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.
RESULTS: 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 TH2 and TH17 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.
CONCLUSIONS: Taken together, our data have shown that URVI enhances the allergic inflammatory response and AHR through a B cell‒monocyte regulatory axis.
摘要：
背景：上呼吸道病毒感染（URVIs）导致80%的哮喘急性发作。然而,潜在的机制仍然知之甚少。
方法：在本研究中，我们使用了URVI小鼠模型,并研究了URVI对哮喘表型的影响和潜在机制.
结果：以前，我们报道，呼吸道合胞病毒（RSV）的鼻腔限制性感染仅产生轻度鼻窦炎症和粘液产生，不会引起直接肺部感染.然而,这种鼻腔限制性感染显著增强了屋尘螨(HDM)诱导的哮喘小鼠肺部TH2和TH17炎症反应,并增加了气道高反应性(AHR).此外,RSV的鼻限制性感染可将Ly6C炎性单核细胞（IMs）招募到有和没有HDM诱导的哮喘的小鼠的肺中。单核细胞趋化因子的表达，包括CCL2和CCL7，也增加了。有趣的是,在IM耗尽的小鼠和CCR2-/-小鼠中，鼻病毒感染诱导的AHR被废除，提示招募的IM在鼻部病毒感染诱导的小鼠哮喘发作中起关键作用。最后,我们观察到,与对照组相比,缺乏B细胞的小鼠在URVI后Ly6C+IMs的募集被消除,并且RSV的鼻限制性感染增加了小鼠肺中CCL2+CCL7+B细胞的数量.
结论：综合来看，我们的数据显示URVI通过B细胞-单核细胞调节轴增强过敏性炎症反应和AHR.
方法：在本研究中，我们使用了URVI小鼠模型,并研究了URVI对哮喘表型的影响和潜在机制.
结果：以前，我们报道，呼吸道合胞病毒（RSV）的鼻腔限制性感染仅产生轻度鼻窦炎症和粘液产生，不会引起直接肺部感染.然而,这种鼻腔限制性感染显著增强了屋尘螨(HDM)诱导的哮喘小鼠肺部TH2和TH17炎症反应,并增加了气道高反应性(AHR).此外,RSV的鼻限制性感染可将Ly6C炎性单核细胞（IMs）招募到有和没有HDM诱导的哮喘的小鼠的肺中。单核细胞趋化因子的表达，包括CCL2和CCL7，也增加了。有趣的是,在IM耗尽的小鼠和CCR2-/-小鼠中，鼻病毒感染诱导的AHR被废除，提示招募的IM在鼻部病毒感染诱导的小鼠哮喘发作中起关键作用。最后,我们观察到,与对照组相比,缺乏B细胞的小鼠在URVI后Ly6C+IMs的募集被消除,并且RSV的鼻限制性感染增加了小鼠肺中CCL2+CCL7+B细胞的数量.
结论：综合来看，我们的数据显示URVI通过B细胞-单核细胞调节轴增强过敏性炎症反应和AHR.
