Acute, but Not Resolved, Influenza A Infection Enhances Susceptibility to House Dust Mite-Induced Allergic Disease
Acute, but Not Resolved, Influenza A Infection Enhances Susceptibility to House Dust Mite-Induced Allergic Disease
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DOI：
10.4049/jimmunol.0802837
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Jordana, Manel
中科院分区：
文献类型：
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作者：
Al-Garawi, Amal A.;Fattouh, Ramzi;Jordana, Manel
呼吸道病毒感染对哮喘表型出现的影响是深入研究的主题。大多数解决这一问题的实验研究使用了惰性Ag OVA，结果存在争议。我们研究了在A型流感感染过程中暴露于低剂量常见空气过敏原屋尘螨（HDM）的后果。首先，我们描述了鼻内感染A/PR 8/34流感病毒后小鼠肺部免疫炎症反应的动力学。我们的数据表明，在第一个10天的峰值响应，相当大的，但不是完全解决在感染后39天（p.i.）。在感染后第7天，小鼠鼻内暴露于HDM连续10天。我们观察到显著增强的嗜酸性粒细胞炎症，Th 2细胞的扩增，增强的HDM特异性IgE和IgG 1反应和增加的粘液产生。此外，肺单核细胞产生增强的IFN-γ和IL-5，不变的IL-13和减少的IL-4。这些免疫和结构变化导致显著的肺功能障碍。当浆细胞样树突状细胞优先于髓样树突状细胞、活化的CD 8（+）T细胞和增加的IFN-γ产生时，这种过敏表型发生，所有这些都被提出来抑制过敏反应。相比之下，HDM引起的炎症反应减少时，暴露发生在解决阶段（第40天p.i.）。有趣的是，这与致敏性降低无关。因此，在急性甲型流感感染期间建立的促炎环境增强了对低剂量HDM的Th 2极化免疫，并沉淀了显著的肺功能障碍。免疫学杂志，2009，182：3095-3104.
The impact of respiratory viral infections on the emergence of the asthmatic phenotype is it subject of intense investigation. Most experimental studies addressing this issue have used the inert Ag OVA with controversial results. We examined the consequences of exposure to a low dose of the common aeroallergen house dust mite (HDM) during the course of an influenza A infection. First, we delineated the kinetics of the immune-inflammatory response in the lung of mice following intranasal infection with influenza A/PR8/34. Our data demonstrate a peak response during the first 10 days, with considerable albeit not complete resolution at day 39 postinfection (p.i.). At day 7 p.i., mice were exposed, intranasally, to HDM for 10 consecutive days. We observed significantly enhanced eosinophilic inflammation, an expansion in Th2 cells, enhanced HDM-specific IgE and IgG1 responses and increased mucous production. Furthermore, lung mononuclear cells produced enhanced IFN-gamma and IL-5, unchanged IL-13, and reduced IL-4. These immunologic and structural changes lead to marked lung dysfunction. This allergic phenotype occurs at a time when there is a preferential increase in plasmacytoid dendritic cells over myeloid dendritic cells, activated CD8(+) T cells, and increased IFN-gamma production, all of which have been proposed to inhibit allergic responses. In contrast, the inflammatory response elicited by HDM was reduced when exposure occurred during the resolution phase (day 40 p.i.). Interestingly, this was not associated with a reduction in sensitization. Thus, the proinflammatory environment established during an acute influenza A infection enhances Th2-polarized immunity to a low dose of HDM and precipitates marked lung dysfunction. The Journal of Immunology, 2009, 182: 3095-3104.