Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus.
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哮喘支气管上皮细胞对鼻病毒感染的先天免疫反应不足。
DOI：
10.1084/jem.20041901
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发表时间：
2005-03-21
期刊：
影响因子：
--
通讯作者：
Davies DE
中科院分区：
文献类型：
--
作者：
Wark PA;Johnston SL;Bucchieri F;Powell R;Puddicombe S;Laza-Stanca V;Holgate ST;Davies DE
鼻病毒是急性哮喘发作的主要诱因，哮喘患者更容易受到这些感染。为了研究这种易感性增加的潜在机制，我们检测了哮喘和健康对照的原代支气管上皮细胞对鼻病毒(RV)-16感染的病毒复制和先天反应。与健康对照相比，哮喘细胞的病毒RNA表达和病毒释放上清分别增加了50倍和7倍。病毒感染在哮喘细胞中诱导细胞晚期裂解，而在正常细胞中不发生。对感染的早期细胞反应的检查显示，在哮喘培养物中，病毒诱导的caspase 3/7活性和凋亡反应受损。在正常培养物中抑制细胞凋亡导致病毒产量增加，与在感染哮喘培养物中看到的结果相当。对早期先天免疫反应的检查显示，哮喘培养物中病毒诱导的干扰素-β mRNA表达严重受损，干扰素-β蛋白的产生减少了2.5倍。在感染的哮喘细胞中，外源性干扰素-β诱导细胞凋亡和病毒复制减少，表明干扰素-β缺乏、细胞凋亡受损和病毒复制增加之间存在因果关系。这些数据提示I型干扰素在治疗或预防病毒引起的哮喘加重中的新用途。
Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
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