Mycobacterium tuberculosis Infection Induces Low-Density Granulocyte Generation by Promoting Neutrophil Extracellular Trap Formation via ROS Pathway
Mycobacterium tuberculosis Infection Induces Low-Density Granulocyte Generation by Promoting Neutrophil Extracellular Trap Formation via ROS Pathway
复制标题
结核分枝杆菌感染通过 ROS 途径促进中性粒细胞胞外陷阱形成，诱导低密度粒细胞生成
DOI：
10.3389/fmicb.2019.01468
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发表时间：
2019-07-11
影响因子：
5.2
通讯作者：
Li, Jun-ming
中科院分区：
文献类型：
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作者：
Su, Rigu;Peng, Yi-ping;Li, Jun-ming
低密度粒细胞（LDG）的作用和特征最近引起了人们的关注，但LDG的形成机制尚不清楚。在我们之前的一项研究中，LDG的频率在结核病患者的外周血中显著升高，并且在结核分枝杆菌感染后原位活化有助于LDG的产生。然而，潜在的分子机制尚未阐明。在本研究中，中性粒细胞胞外陷阱（NETs）的释放和ROS水平在正常密度粒细胞（NDG）被M感染之前受到调节。结核病，随后还监测了NDG向LDG的转化。结果表明，结核病相关LDG自发释放高水平的NET。促进NET的释放导致M的NDG向LDG转化的增加。结核感染，同时抑制NET的释放抑制了感染后的这种转化。分枝结核感染显著增加了中性粒细胞中的ROS水平和NDG向LDG的转化。清除ROS或阻断ROS的产生。结核病感染的NDG显着抑制NET的释放并阻止LDG的产生。此外，在不影响ROS水平的情况下抑制NET的形成显著降低了M后NDG向LDG的转化。肺结核感染。总体而言，本研究表明，M。结核杆菌可通过ROS途径促进NET的释放，从而诱导LDGs的产生。
The roles and characteristics of low-density granulocytes (LDGs) have recently attracted attention; however, the mechanism of the formation of LDGs is yet unclear. In one of our previous studies, the frequency of LDGs was significantly elevated in the peripheral blood of tuberculosis patients, and in situ activation contributed to the generation of LDGs upon Mycobacterium tuberculosis infection. However, the underlying molecular mechanisms are yet to be elucidated. In the present study, the release of neutrophil extracellular traps (NETs) and the levels of ROS were regulated before the normal-density granulocytes (NDGs) to be infected with M. tuberculosis, and the conversion of NDGs to LDGs was monitored subsequently as well. The results showed that tuberculosis-related LDGs spontaneously released high levels of NETs. Promoting the release of NETs led to increase in the conversion of NDGs to LDGs in M. tuberculosis infection, while inhibiting the release of NETs suppressed this conversion after the infection. The M. tuberculosis infection significantly increased the ROS levels in neutrophils and the conversion of NDGs to LDGs. Scavenging ROS or blocking the ROS generation of M. tuberculosis-infected NDGs significantly suppressed the release of NETs and blocked the generation of LDGs. Moreover, inhibiting the formation of NETs without affecting the levels of ROS significantly decreased the conversion of NDGs to LDGs after M. tuberculosis infection. Overall, this study demonstrated that M. tuberculosis could induce the generation of LDGs by promoting the release of NET via ROS pathway.