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Influenza A virus infection augments airway sensitization in mice

甲型流感病毒感染增强小鼠气道敏感性

基本信息

批准号：
12670568
负责人：
SUZUKI Shunsuke
金额：
$ 1.98万
依托单位：
Yokohama City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

在流行病学上，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生感染型哮喘，但其发病机制尚不清楚。以前，我们证明了甲型流感病毒感染可增强小鼠对吸入抗原的敏感性和气道反应性（JACI 102 ; 732，1998）。在本研究中，我们研究了流感病毒A感染时吸入抗原（包括抗原呈递细胞）增强致敏的机制，我们通过雾化吸入应用抗原（卵清蛋白），因为这种吸入致敏技术可能更恰当地反映人类哮喘发展中的实际致敏途径。BALB/c小鼠鼻内接种流感A/Guizhou-X/H3 N2。在感染的急性期，动物暴露于卵清蛋白（OVA）的气溶胶中。两周后，气道反应性（AR）增加，OVA特异性IgE和Th 2细胞因子水平也升高。在组织学上，支气管上皮上观察到树突状细胞，并且OA捕获树突状细胞迁移到区域淋巴结。在恢复期吸入OA既不产生OA特异性IgE，也不将树突状细胞迁移到支气管。在感染急性期的细胞因子和趋化因子分析中，IFN-γ增加至感染后第7天，TNF-α、MIP-2和KC在第3天增加最大。而IL-4、IL-5等Th 2型细胞因子在病毒感染后没有发生变化，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细胞表面，捕获吸入的抗原，产生2型免疫应答。然而，树突状细胞的刺激机制仍然是未知的。