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首页> 外文期刊>American Journal of Physiology >Antiviral immunity is impaired in COPD patients with frequent exacerbations
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Antiviral immunity is impaired in COPD patients with frequent exacerbations

机译：在COPD患者频繁加剧的COPD患者中受到抗病毒免疫力

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Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during vims-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>=2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations.
机译：频繁加剧的患者代表了一种慢性阻塞性肺病（COPD）亚组，需要更好的治疗方案。本研究的目的是确定常见于COPD频繁恶化的易感性的先天免疫机制。我们在稳定状态下和Vims相关的加剧期间测量了来自COPD患者的样品中免疫介质和细菌载体的痰表达。另外评估对来自COPD患者的分化的原发性支气管上皮细胞（BECS）对rhinovirus感染的体外免疫应答。患者被分层为频繁的恶化剂（上一年中的2个恶化）或不常见的恶化者（前一年中的<2加剧），在这些群体之间进行了比较。频繁的恶性剂在临床稳定和病毒相关的加剧期间，耐药免疫介质型I和III干扰剂的表达降低了抗病毒免疫介质型I和III干扰素的表达，并减少了干扰素刺激的基因（ISG）表达。鉴定了对上皮细胞固有的先天性灭绝剂的作用：在体外鼻病毒（RV）感染期间的干扰素和ISG的诱导也受到频繁加剧器的分化。在病毒相关的加热发生后，常见的恶化剂另外增加了2 WK的痰细菌载荷。这些数据涉及涉及在一些COPD患者中观察到的加剧性倾向的上皮细胞的缺乏气道直接免疫。在肺部促进先天抗微生物免疫力的治疗方法可能是可行的预防和治疗频繁恶化的可行策略。

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