Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice.
Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice.
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DOI：
10.1186/1465-9921-11-14
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发表时间：
2010-02-03
影响因子：
5.8
通讯作者：
Kumar RK
中科院分区：
文献类型：
--
作者：
Siegle JS;Hansbro N;Herbert C;Rosenberg HF;Domachowske JB;Asquith KL;Foster PS;Kumar RK
生命早期的呼吸道病毒感染，尤其是呼吸道合胞病毒（RSV）感染，会增加儿童后续患哮喘的风险。本研究的目的是评估生命早期感染一种针对RSV的物种特异性模型病毒以及随后接触过敏原是否易诱发哮喘特征的出现。
我们采用了一种独特的动物模型组合，即BALB/c小鼠在新生期感染小鼠肺炎病毒（PVM，它能在人类婴儿中复制严重的RSV疾病），在恢复后，用卵清蛋白进行鼻内致敏。动物接受为期4周的气雾化抗原低水平激发以引发慢性哮喘的变化，随后进行一次中等水平激发以诱导炎症加重。然后我们评估了气道炎症、具有重塑特征的上皮变化、气道高反应性（AHR）以及宿主的免疫反应。
过敏性气道炎症，包括嗜酸性粒细胞的募集，仅在从新生期PVM感染中恢复且随后被致敏并长期接受抗原激发的动物中显著存在。此外，只有这些小鼠表现出增强的Th2偏向性免疫反应，包括抗卵清蛋白IgE和IgG1血清水平升高以及Th2相关细胞因子IL - 4、IL - 5和IL - 13相对表达增加。相比之下，AHR的发展和黏液细胞变化与从PVM感染中恢复有关，而与随后的过敏原激发无关。在PVM感染后的肺部可检测到IL - 25表达增加，这可能有助于诱导Th2反应。通过IL - 4受体α链的信号传导对过敏性炎症、黏液细胞变化和AHR的发展至关重要，因为在受体缺陷小鼠中所有这些情况都不存在。相反，重塑变化在接受长期过敏原激发的小鼠中明显，无论是否有新生期PVM感染，并且不依赖于通过IL - 4受体的信号传导。
在这个小鼠模型中，生命早期病毒感染与过敏原致敏/激发之间的相互作用对儿童哮喘特征的发展至关重要，包括过敏性炎症和Th2偏向性免疫反应。
Early-life respiratory viral infections, notably with respiratory syncytial virus (RSV), increase the risk of subsequent development of childhood asthma. The purpose of this study was to assess whether early-life infection with a species-specific model of RSV and subsequent allergen exposure predisposed to the development of features of asthma. We employed a unique combination of animal models in which BALB/c mice were neonatally infected with pneumonia virus of mice (PVM, which replicates severe RSV disease in human infants) and following recovery, were intranasally sensitised with ovalbumin. Animals received low-level challenge with aerosolised antigen for 4 weeks to elicit changes of chronic asthma, followed by a single moderate-level challenge to induce an exacerbation of inflammation. We then assessed airway inflammation, epithelial changes characteristic of remodelling, airway hyperresponsiveness (AHR) and host immunological responses. Allergic airway inflammation, including recruitment of eosinophils, was prominent only in animals that had recovered from neonatal infection with PVM and then been sensitised and chronically challenged with antigen. Furthermore, only these mice exhibited an augmented Th2-biased immune response, including elevated serum levels of anti-ovalbumin IgE and IgG1 as well as increased relative expression of Th2-associated cytokines IL-4, IL-5 and IL-13. By comparison, development of AHR and mucous cell change were associated with recovery from PVM infection, regardless of subsequent allergen challenge. Increased expression of IL-25, which could contribute to induction of a Th2 response, was demonstrable in the lung following PVM infection. Signalling via the IL-4 receptor α chain was crucial to the development of allergic inflammation, mucous cell change and AHR, because all of these were absent in receptor-deficient mice. In contrast, changes of remodelling were evident in mice that received chronic allergen challenge, regardless of neonatal PVM infection, and were not dependent on signalling via the IL-4 receptor. In this mouse model, interaction between early-life viral infection and allergen sensitisation/challenge is essential for development of the characteristic features of childhood asthma, including allergic inflammation and a Th2-biased immune response.
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影响因子：
3
作者：
Bonville CA;Percopo CM;Dyer KD;Gao J;Prussin C;Foster B;Rosenberg HF;Domachowske JB
通讯作者：
Domachowske JB
影响因子：
4.4
作者：
Garvey, TL;Dyer, KD;Rosenberg, HF
通讯作者：
Rosenberg, HF
影响因子：
4.4
作者：
Dakhama, A;Park, JW;Gelfand, EW
通讯作者：
Gelfand, EW
影响因子：
14.2
作者：
Gerhold, K;Bluemchen, K;Hamelmann, E
通讯作者：
Hamelmann, E
DOI：
10.1513/pats.200502-015aw
发表时间：
2005-01-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Holtzman, Michael J;Tyner, Jeffrey W;Zhang, Yong
通讯作者：
Zhang, Yong