Influenza A virus infection augments airway sensitization in mice

从流行病学来看，呼吸道病毒感染是婴儿和成人哮喘患者喘息的主要原因。呼吸道病毒感染后可发展为感染型哮喘，但其发病机制尚不清楚。此前，我们在小鼠中证明，感染甲型流感病毒会增强对吸入抗原的敏感度和呼吸道反应性(JACI 102；732,1998)。在本研究中，我们研究了甲型流感病毒感染中对包括抗原提呈细胞在内的吸入性抗原的增敏机制。我们通过雾化吸入的方式应用了一种抗原(卵清蛋白)，因为这种吸入性致敏技术可以更好地反映人类哮喘发生发展中的实际致敏途径。BALB/c小鼠鼻腔接种甲型流感病毒贵州X/H3N2。在感染的急性期，动物暴露在卵清蛋白(OVA)的气雾剂中。两周后，气道反应性(AR)增加，OVA特异性IgE和Th2细胞因子水平也升高。组织学上，在支气管上皮上可观察到树突状细胞，捕获OA的树突状细胞迁移到区域淋巴结。在恢复期吸入OA既没有产生OA特异性的IgE，也没有将树突状细胞迁移到支气管。在感染急性期细胞因子和趋化因子的分析中，干扰素-ν在感染后第7天开始升高，其中肿瘤坏死因子-α、巨噬细胞抑制蛋白-2和KC在感染后第3天达到最大值，而Th2型细胞因子如IL-4和IL-5没有变化，IL-12也没有增加，因此在病毒感染急性期，树突状细胞出现在支气管上皮并捕获吸入性抗原，从而产生2型免疫应答。然而，树突状细胞的刺激机制仍不清楚。

Epidemiologically, respiratory viral infections are a major cause of wheezing in infants and adult patients with asthma. Infectious type of asthma may develop after respiratory viral infection, although its mechanism is still unknown. Previously, we demonstrated that infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice (JACI 102 ; 732, 1998). In the present study, we studied the mechanism of enhanced sensitization to inhaled antigen, including antigen-presenting cells, in influenza A virus infection.We applied an antigen (ovalbumin) by aerosol inhalation, because this inhalation sensitization technique may reflect more appropriately the actual route of sensitization in the development of human asthma. BALB/c mice were inoculated intranasally with Influenza A/Guizhou-X/H3N2. Animals were exposed to aerosols of ovalbumin (OVA) during the acute phase of the infection. Two weeks later, airway responsiveness (AR) was increased and both levels of OVA-specific IgE and Th2 cytokines were also rose. Histologically, dendritic cells were observed on the bronchial epithelium and OA-capturing dendritic cells migrated to the regional lymphnodes. OA inhalation during the recovery phase did neither produce OA-specific IgE and migrate dendritic cells to the bronchi. In analysis of cytokines and chemokines during the acute phase of infection, IFN-ν increased upto day 7 postinfection, and TNF-α, MIP-2 and KC increased maximally on day 3. However, Th2 cytokines such as IL-4 and IL-5 did not show any change by viral infection, and also IL-12 did not increase.Therefore, during the acute phase of viral infection, the dendritic cells appear to the bronchial epithelium and capture inhaled antigens, resulting in type 2 immune response. However, the mechanism of stimulation of the dendritic cells is still unknown.