Mycobacterium tuberculosis triggers apoptosis in peripheral neutrophils involving toll-like receptor 2 and p38 mitogen protein kinase in tuberculosis patients
Mycobacterium tuberculosis triggers apoptosis in peripheral neutrophils involving toll-like receptor 2 and p38 mitogen protein kinase in tuberculosis patients
复制标题
DOI：
10.1128/iai.72.9.5150-5158.2004
复制
发表时间：
2004-09-01
影响因子：
3.1
通讯作者：
Sasiain, MC
中科院分区：
文献类型：
--
作者：
Alemán, M;Schierloh, P;Sasiain, MC
暴露于结核分枝杆菌的多形核中性粒细胞（PMN）表现出杀菌反应并产生炎症蛋白。这种中性粒细胞介导的炎症反应是通过凋亡程序的激活来调节的，该程序共同避免组织损伤。在体外，来自结核病 (TB) 患者的循环 PMN 显示出自发性细胞凋亡增加，并且结核分枝杆菌诱导的激活加速了 PMN 细胞凋亡。在这项研究中，我们评估了自发性和结核分枝杆菌诱导的细胞凋亡的机制。我们证明 PMN 的凋亡不是由脂阿拉伯甘露聚糖或结核分枝杆菌的全细胞裂解物诱导的，并且肿瘤坏死因子 α、CD11b、CD14 和 Fcgamma 受体都不参与其中。活动性结核病患者的中性粒细胞凋亡 (TB-PMN) 是通过 Toll 样受体 2 (TLR2) 与整个结核分枝杆菌相互作用诱导的，与自发性凋亡相反，它涉及 p38 丝裂原激活蛋白激酶 (MAPK) 途径。这些结果与循环 TB-PMN 中磷酸化 p38 (p-p38) 的高表达以及结核分枝杆菌体外诱导 PMN 中 p-p38 表达的能力相关。因此，当细菌负荷较低时，TB-PMN 可以通过 TLR2 检测非调理作用的结核分枝杆菌，从而激活 p38 MAPK 通路，进而诱导 PMN 激活和凋亡。这一机制还需要在感染部位进一步证实。
Polymorphonuclear neutrophils (PMN) exposed to Mycobacterium tuberculosis display bactericidal responses and produce inflammatory proteins. This PMN-mediated inflammatory response is regulated by an activation of the apoptotic program, which collaborates to avoid tissue injury. In vitro, circulating PMN from patients with tuberculosis (TB) show an increased spontaneous apoptosis, and M. tuberculosis-induced activation accelerates the PMN apoptosis. In this study, we evaluated the mechanisms involved in spontaneous and M. tuberculosis-induced apoptosis. We demonstrate that apoptosis of PMN is not induced by lipoarabinomannan or by a whole-cell lysate of M. tuberculosis and that neither tumor necrosis factor alpha nor CD11b, CD14, and Fcgamma receptors are involved. Apoptosis of PMN from patients with active TB (TB-PMN) is induced by the interaction with the whole M. tuberculosis via Toll-like receptor 2 (TLR2), and, in contrast to spontaneous apoptosis, it involves the p38 mitogen-activated protein kinase (MAPK) pathway. These results correlate with a high expression of phosphorylated p38 (p-p38) in circulating TB-PMN and with the ability of M. tuberculosis to induce in vitro the expression of p-p38 in PMN. Therefore, when the bacterial burden is low, TB-PMN could be detecting nonopsonized M. tuberculosis via TLR2, leading to the activation of the p38 MAPK pathway, which in turn would induce PMN activation and apoptosis. This mechanism needs further confirmation at the site of infection.