Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease.
Human rhinovirus proteinase 2A induces TH1 and TH2 immunity in patients with chronic obstructive pulmonary disease.
复制标题
DOI：
10.1016/j.jaci.2010.02.035
复制
发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Kheradmand F
中科院分区：
文献类型：
--
作者：
Singh M;Lee SH;Porter P;Xu C;Ohno A;Atmar RL;Greenberg SB;Bandi V;Gern J;Amineva S;Aminev A;Skern T;Smithwick P;Perusich S;Barrow N;Roberts L;Corry DB;Kheradmand F
与烟草有关的肺部疾病，包括慢性阻塞性肺疾病(COPD)，是全世界与肺相关的残疾和死亡的主要原因。慢性阻塞性肺疾病急性加重(AE-COPD)通常与上呼吸道和下呼吸道病毒感染有关，在患有晚期肺部疾病的人中可导致呼吸衰竭。我们试图确定COPD恶化的机制和宿主对病原体衍生因子的反应。在24个月的时间里，我们评估了COPD患者(n=155)和对照组(n=103)上、下呼吸道感染的病毒原因。我们收集了基线和加重状态下的鼻腔和支气管肺泡灌洗液和外周血。我们研究了人鼻病毒(HRV)蛋白水解酶对人和小鼠T细胞活化的影响。HRV是从AE-COPD患者的鼻液和肺液中分离出来的。COPD患者急性感染时肺泡灌洗液和CD4T细胞均表现为TH1和TH2细胞因子表型。HRV编码的蛋白酶2A在体外激活单核细胞来源的树突状细胞，并诱导CD4T细胞产生强大的TH1和TH2免疫反应。重组鼻病毒蛋白酶2A鼻腔给药后，小鼠的呼吸道高反应性、肺部炎症及CD4T细胞分泌IL-4和干扰素-γ均明显增加。我们的研究结果表明，重度COPD患者在AE-COPD期间表现出TH1和TH2偏向的反应。HRV编码的蛋白水解酶2A和其他微生物蛋白一样，可以在重度COPD患者的上呼吸道和下呼吸道感染中提供TH1和TH2偏向的佐剂因子。COPD患者对分泌型病毒蛋白水解酶免疫应答的改变可能是导致呼吸困难和呼吸衰竭加重的原因之一。
Tobacco-related lung diseases, including chronic obstructive pulmonary disease (COPD), are major causes of lung-related disability and death worldwide. Acute exacerbation of COPD (AE-COPD) is commonly associated with upper and lower respiratory tract viral infections and can result in respiratory failure in those with advanced lung disease. We sought to determine the mechanism underlying COPD exacerbation and host response to pathogen-derived factors. Over a 24-month period, we assessed the viral causes for upper and lower respiratory tract infections in patients with COPD (n = 155) and control subjects (n = 103). We collected nasal and bronchoalveolar lavage fluid and peripheral blood under baseline and exacerbated conditions. We determined the effect of human rhinovirus (HRV) proteinases on T-cell activation in human subjects and mice. HRVs are isolated from nasal and lung fluid from subjects with AE-COPD. Bronchoalveolar lavage fluid and CD4 T cells from patients with COPD exhibited a TH1 and TH2 cell cytokine phenotype during acute infection. HRV-encoded proteinase 2A activated monocyte-derived dendritic cells in vitro and induced strong TH1 and TH2 immune responses from CD4 T cells. Intranasal administration of recombinant rhinovirus proteinase 2A in mice resulted in an increase in airway hyperreactivity, lung inflammation, and IL-4 and IFN-γ production from CD4 T cells. Our findings suggest that patients with severe COPD show TH1- and TH2-biased responses during AE-COPD. HRV-encoded proteinase 2A, like other microbial proteinases, could provide a TH1- and TH2-biasing adjuvant factor during upper and lower respiratory tract infection in patients with severe COPD. Alteration of the immune response to secreted viral proteinases might contribute to worsening of dyspnea and respiratory failure in patients with COPD.
登录
查看更多内容
影响因子：
14.2
作者：
Kiss, Attila;Montes, Martin;Corry, David B.
通讯作者：
Corry, David B.
DOI：
10.1164/rccm.200207-756ws
发表时间：
2003-04-15
影响因子：
24.7
作者：
Croxton, TL;Weinmann, GG;Buist, AS
通讯作者：
Buist, AS
DOI：
10.1164/ajrccm.164.11.2104093
发表时间：
2001-12-01
影响因子：
24.7
作者：
Bandi, V;Apicella, MA;Greenberg, SB
通讯作者：
Greenberg, SB
影响因子：
15.9
作者：
Kim, CH;Rott, L;Butcher, EC
通讯作者：
Butcher, EC
影响因子：
30.5
作者：
Corry, DB;Rishi, K;Kheradmand, F
通讯作者：
Kheradmand, F