病毒诱导的急性哮喘患者中自然免疫信号受体特征
2011/03/24
摘要
背景：Toll样受体(TLRs)与自然免疫活化在临床哮喘恶化中的作用及两者与病毒感染的关系尚不清楚。
目的：本试验在病毒感染诱发的急性哮喘患者中，研究TLR表达和自然免疫活性的特征。
方法：研究对象为急性哮喘患者、稳定期哮喘患者和健康受试者。对所有研究对象检测肺活量，同时采用等渗盐水诱导痰液。痰液中加入二硫苏糖醇，计数总白细胞和白细胞分类。同时，采用实时PCR检测痰液中的TLR2、TLR3、TLR4、IL-10和IP-10。痰液上清液用于检测自然免疫标志物，其中包括IL-8、基质金属蛋白酶-9和中性粒细胞弹性酶活性。采用实时和基于凝胶的PCR检测病毒。
结果：与健康对照相比，急性哮喘和稳定期哮喘患者痰液TLR2表达均上调，哮喘急性恶化后4～6周逐渐下降。与非病毒感染的急性哮喘患者相比，病毒感染的急性哮喘患者痰液TLR2表达上调。然而，健康对照、稳定期哮喘患者和急性哮喘患者间在TLR3表达上无显著差异。在急性哮喘患者，病毒感染患者的TLR3表达显著高于无病毒感染患者。此外，病毒感染的急性哮喘患者，痰液中的IP-10和IL-10表达高于无病毒感染的急性哮喘患者。对于病毒诱发的急性哮喘，IP-10和IL-10表达与TLR2和TLR3表达相关。
结论和临床相关性：病毒诱发的急性哮喘患者能特异性诱导TLR2、TLR3、IP-10和IL-10表达，这表明，病毒诱发的哮喘恶化中，TLR介导的信号，通过自然免疫和适应性免疫途径，在哮喘气道炎症中起到重要作用。这些介质有可能成为病毒诱发哮喘的治疗的靶点。同时，这些介质也有助于诊断急性哮喘恶化和监测哮喘治疗反应，帮助控制哮喘恶化。
（刘国梁 审校）
Clin Exp Allergy. 2010 Dec 3. doi: 10.1111/j.1365-2222.2010.03669.x. [Epub ahead of print]
Characterization of innate immune signalling receptors in virus-induced acute asthma.
Wood LG, Simpson JL, Wark PA, Powell H, Gibson PG.
Centre for Asthma and Respiratory Diseases, University of Newcastle, Callaghan, NSW, Australia Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
Abstract
Background The role of toll-like receptors (TLRs) and innate immune activation in clinical asthma exacerbations and their relationship to virus infection are unclear. Objective This study aimed to characterize TLR expression and innate immune activity during virus infection in acute asthma. Methods Subjects with acute asthma, stable asthma and healthy controls were recruited and underwent spirometry and sputum induction with isotonic saline. Selected sputum was dispersed with dithiothreitol and total and differential leucocyte counts were performed. Selected sputum was also used for quantitative real-time PCR for TLR2, TLR3, TLR4, IL-10 and IP-10mRNA expression. Sputum supernatant was used for the measurement of innate immune markers, including IL-8, matrix metalloproteinase-9 and neutrophil elastase activity. Viruses were detected using real-time and gel-based PCR. Results Sputum TLR2 mRNA expression was up-regulated in both acute and stable asthma compared with healthy controls and decreased 4-6 weeks after acute exacerbation. Sputum TLR2 mRNA expression was elevated in viral, compared with non-viral, acute asthma. Sputum TLR3 mRNA expression was similar in controls, stable and acute asthma. However, in acute asthma, subjects with virus-induced acute asthma had significantly higher sputum TLR3 mRNA expression. Induced sputum gene expression for IP-10 and IL-10 were increased in viral, compared with non-viral, acute asthma. In virus-induced acute asthma, levels of IP-10 and IL-10 mRNA expression were correlated with the mRNA expression of TLR2 and TLR3. Conclusions and Clinical Relevance Virus-induced acute asthma leads to specific induction of TLR2, TLR3, IP-10 and IL-10, suggesting that signalling via TLRs may play an important role in mediating airway inflammation, via both innate and adaptive pathways, in virus-induced exacerbations. These mediators may provide potential treatment targets for virus-induced asthma. They may also be useful in diagnosing the nature of acute asthma exacerbations and monitoring treatment responses, which would be useful in the clinical management of asthma exacerbations.
Clin Exp Allergy. 2010 Dec 3. doi: 10.1111/j.1365-2222.2010.03669.x. [Epub ahead of print]
背景：Toll样受体(TLRs)与自然免疫活化在临床哮喘恶化中的作用及两者与病毒感染的关系尚不清楚。
目的：本试验在病毒感染诱发的急性哮喘患者中，研究TLR表达和自然免疫活性的特征。
方法：研究对象为急性哮喘患者、稳定期哮喘患者和健康受试者。对所有研究对象检测肺活量，同时采用等渗盐水诱导痰液。痰液中加入二硫苏糖醇，计数总白细胞和白细胞分类。同时，采用实时PCR检测痰液中的TLR2、TLR3、TLR4、IL-10和IP-10。痰液上清液用于检测自然免疫标志物，其中包括IL-8、基质金属蛋白酶-9和中性粒细胞弹性酶活性。采用实时和基于凝胶的PCR检测病毒。
结果：与健康对照相比，急性哮喘和稳定期哮喘患者痰液TLR2表达均上调，哮喘急性恶化后4～6周逐渐下降。与非病毒感染的急性哮喘患者相比，病毒感染的急性哮喘患者痰液TLR2表达上调。然而，健康对照、稳定期哮喘患者和急性哮喘患者间在TLR3表达上无显著差异。在急性哮喘患者，病毒感染患者的TLR3表达显著高于无病毒感染患者。此外，病毒感染的急性哮喘患者，痰液中的IP-10和IL-10表达高于无病毒感染的急性哮喘患者。对于病毒诱发的急性哮喘，IP-10和IL-10表达与TLR2和TLR3表达相关。
结论和临床相关性：病毒诱发的急性哮喘患者能特异性诱导TLR2、TLR3、IP-10和IL-10表达，这表明，病毒诱发的哮喘恶化中，TLR介导的信号，通过自然免疫和适应性免疫途径，在哮喘气道炎症中起到重要作用。这些介质有可能成为病毒诱发哮喘的治疗的靶点。同时，这些介质也有助于诊断急性哮喘恶化和监测哮喘治疗反应，帮助控制哮喘恶化。
（刘国梁 审校）
Clin Exp Allergy. 2010 Dec 3. doi: 10.1111/j.1365-2222.2010.03669.x. [Epub ahead of print]
Characterization of innate immune signalling receptors in virus-induced acute asthma.
Wood LG, Simpson JL, Wark PA, Powell H, Gibson PG.
Centre for Asthma and Respiratory Diseases, University of Newcastle, Callaghan, NSW, Australia Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
Abstract
Background The role of toll-like receptors (TLRs) and innate immune activation in clinical asthma exacerbations and their relationship to virus infection are unclear. Objective This study aimed to characterize TLR expression and innate immune activity during virus infection in acute asthma. Methods Subjects with acute asthma, stable asthma and healthy controls were recruited and underwent spirometry and sputum induction with isotonic saline. Selected sputum was dispersed with dithiothreitol and total and differential leucocyte counts were performed. Selected sputum was also used for quantitative real-time PCR for TLR2, TLR3, TLR4, IL-10 and IP-10mRNA expression. Sputum supernatant was used for the measurement of innate immune markers, including IL-8, matrix metalloproteinase-9 and neutrophil elastase activity. Viruses were detected using real-time and gel-based PCR. Results Sputum TLR2 mRNA expression was up-regulated in both acute and stable asthma compared with healthy controls and decreased 4-6 weeks after acute exacerbation. Sputum TLR2 mRNA expression was elevated in viral, compared with non-viral, acute asthma. Sputum TLR3 mRNA expression was similar in controls, stable and acute asthma. However, in acute asthma, subjects with virus-induced acute asthma had significantly higher sputum TLR3 mRNA expression. Induced sputum gene expression for IP-10 and IL-10 were increased in viral, compared with non-viral, acute asthma. In virus-induced acute asthma, levels of IP-10 and IL-10 mRNA expression were correlated with the mRNA expression of TLR2 and TLR3. Conclusions and Clinical Relevance Virus-induced acute asthma leads to specific induction of TLR2, TLR3, IP-10 and IL-10, suggesting that signalling via TLRs may play an important role in mediating airway inflammation, via both innate and adaptive pathways, in virus-induced exacerbations. These mediators may provide potential treatment targets for virus-induced asthma. They may also be useful in diagnosing the nature of acute asthma exacerbations and monitoring treatment responses, which would be useful in the clinical management of asthma exacerbations.
Clin Exp Allergy. 2010 Dec 3. doi: 10.1111/j.1365-2222.2010.03669.x. [Epub ahead of print]
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