Impaired CXCR1-dependent oxidative defence in active tuberculosis patients
Impaired CXCR1-dependent oxidative defence in active tuberculosis patients
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DOI：
10.1016/j.tube.2015.07.008
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发表时间：
2015-12-01
期刊：
影响因子：
3.2
通讯作者：
Godaly, Gabriela
中科院分区：
文献类型：
--
作者：
Alaridah, Nader;Winqvist, Niclas;Godaly, Gabriela
在结核病（TB）中发生的明显的宿主炎症反应大多与对入侵病原体的免疫失败有关。g蛋白偶联受体CXCR1和CXCR2参与肺部炎症反应的重要信号转导途径。我们在24例肺结核患者和潜伏性肺结核感染（LTBI）患者的简单全血模型中研究了这些受体的表达和功能。从肺指数患者的密切接触者中招募健康对照。我们发现，与LTBI患者和对照组相比，肺结核患者的血细胞中CXCR1的表达显著增加（p < 0.001）。相比之下，LTBI受试者与肺结核患者（p < 0.001）和对照组（p < 0.01）相比，CXCR2表达显著增加。与LTBI和对照组相比，肺结核患者的白细胞功能（以氧化能力衡量）下降（p < 0.001），并与CXCR1表达增加相关。白细胞募集（以microRNA-223的表达来衡量）在肺结核患者中比在LTBI中增加（p < 0.05）。我们发现受体表达的变化与疾病进展有关，并影响对结核分枝杆菌（Mtb）的免疫反应。(C) 2015年作者。Elsevier Ltd.出版。
Much of the pronounced host inflammatory response that occurs in tuberculosis (TB) is related to failed immunity against the invading pathogen. The G-protein coupled receptors CXCR1 and CXCR2 are implicated in important signal transduction pathways in lung inflammatory responses. We investigated the expression and function of these receptors in a simple whole blood model from 24 patients with pulmonary TB and in subjects with latent TB infection (LTBI). Healthy controls were recruited from close contacts to the pulmonary index patients. We found that pulmonary TB patients had significantly increased CXCR1 expression on blood cells compared to LTBI subjects and controls (p < 0.001). In contrast, LTBI subjects had a significant increase in CXCR2 expression compared to pulmonary TB patients (p < 0.001) and controls (p < 0.01). Leukocyte function, measured as oxidative capacity, was decreased in pulmonary TB patients compared to LTBI and controls (p < 0.001) and correlated with the increased CXCR1 expression. Leukocyte recruitment, measured as the expression of microRNA-223 was increased in pulmonary TB patients compared to LTBI (p < 0.05). We found that variations in receptor expression are linked to disease progression and affect the immune response against Mycobacterium tuberculosis (Mtb). (C) 2015 The Authors. Published by Elsevier Ltd.