Alaridah Nader, Winqvist Niclas, Håkansson Gisela, Tenland Erik, Rönnholm Anna, Sturegård Erik, Björkman Per, Godaly Gabriela
Translational Medicine, Department of Clinical Microbiology, Malmö, Sweden.
Regional Department of Infectious Disease Control and Prevention, Malmö, Sweden; Infectious Disease Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Tuberculosis (Edinb). 2015 Dec;95(6):744-750. doi: 10.1016/j.tube.2015.07.008. Epub 2015 Aug 14.
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).
结核病（TB）中出现的明显宿主炎症反应大多与针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中的重要信号转导途径。我们在24例肺结核患者和潜伏性结核感染（LTBI）患者的简单全血模型中研究了这些受体的表达和功能。健康对照从肺部索引患者的密切接触者中招募。我们发现，与LTBI受试者和对照相比，肺结核患者血细胞上的CXCR1表达显著增加（p<0.001）。相比之下，与肺结核患者（p<0.001）和对照（p<0.01）相比，LTBI受试者的CXCR2表达显著增加。以氧化能力衡量的白细胞功能在肺结核患者中低于LTBI和对照（p<0.001），且与CXCR1表达增加相关。以微小RNA-223表达衡量的白细胞募集在肺结核患者中高于LTBI（p<0.05）。我们发现受体表达的变化与疾病进展相关，并影响针对结核分枝杆菌（Mtb）的免疫反应。
