上下呼吸道疾病关系密切相关，变应性疾病及感染性疾病对下呼吸道疾病均有显著影响，其机制尚未明确。有60%以上的哮喘发作是由上呼吸道病毒感染引起的，但与哮喘发作相关的许多病毒主要导致上呼吸道感染。我们在前期研究中构造鼻冠状病毒感染小鼠模型，发现小鼠肺部有种新的树突状细胞亚型显著增多，而肺部并没有任何病毒存在，在最近的研究中称这种新亚型为炎性树突细胞（infDCs），并发现其在Th2型变应性应答中起到了诱导发生和发展的关键作用。因此，我们假设，鼻病毒感染可以通过增加infDCs的浸润，间接激活肺部先天免疫应答，增强肺中的Th2反应。我们将构造鼻病毒感染小鼠模型，证明鼻病毒感染可间接通过增加infDCs来激活肺部先天免疫，及鼻病毒感染在肺变应性炎症中可诱导infDCs增多，以期阐明上呼吸道病毒感染促进哮喘发作的机制，对进一步揭示上下呼吸道的免疫链接机制有重要意义。

The allergic diseases and the infectious diseases in the upper airway both have significant effects on the lower airway diseases. However, the immunologic mechanism behind this concept remains largely unknown. Upper airway viral infection is responsible for up to 60% of asthma exacerbation.however, clinical observations have shown that many viruses that are associated with asthma exacerbation mainly lead to upper airway infection. .On our preliminary study, we observed that nasal infection by coronavirus significantly increased the infiltration of a new subset of dendritic cells in the lungs without any virus presence in the lungs. The newly defined subset of DCs termed inflammatory dendritic cells (infDCs). Recent studies have shown that the infDCs play a critical role in both the induction and development of Th2 allergic response. We thus hypothesize that nasal viral infection can indirectly prime lung innate immunity by increasing the infiltration of inflammatory dendritic cells, which subsequently enhance the Th2 response in the lungs..We will use this nasal viral infection model to test the hypothesis that nasal viral infection indirectly primes lung innate immunity by increasing the infiltration of inflammatory dendritic cells and induced infiltration of inflammatory dendritic cells in the lungs orchestrates allergic inflammation.This project contributes to elucidate the mechanism of respiratory viral infections and to further reveal the mechanisms of the immunologic link between the upper and lower airways.

上、下气道是一个连续的整体，病毒诱导的哮喘被认为是鼻部炎症间接导致肺部免疫激活的结果。本研究通过冠状病毒MHV-1对小鼠进行鼻部感染，构建MHV-1小鼠鼻部感染模型，运用流式细胞学、RT-PCR、组织学和Western Blot等技术分析小鼠鼻粘膜、肺泡灌洗液、肺匀浆液、外周血及脾脏中的MHV-1、infDCs及细胞因子含量，探讨鼻病毒感染对下呼吸道的作用。并将鼻腔感染小鼠提取的infDCs注入OVA致敏小鼠，再次OVA激发后，检测小鼠肺组织中的细胞因子含量。采用SPSS18.0对实验数据进行随机区组间方差分析，发现鼻部MHV-1感染后小鼠肺内infDCs增多，OVA致敏小鼠用infDCs干预后Th2相关细胞因子IL-4、IL-10上升。MHV-1鼻腔感染不会导致小鼠肺部受病毒侵犯，仅造成肺实质infDCs浸润，可增强Th2免疫应答，导致哮喘加重。本研究探讨了上气道感染及infDCs在哮喘中的作用，为控制哮喘的发生，改善哮喘症状提供了新方向，为进一步研究鼻病毒感染造成肺内infDCs浸润的机制打下了基础。