The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes.
The Defect in Autophagy Induction by Clinical Isolates of Mycobacterium Tuberculosis Is Correlated with Poor Tuberculosis Outcomes.
复制标题
结核分枝杆菌临床分离株诱导自噬的缺陷与不良结核病治疗结果相关。
DOI：
10.1371/journal.pone.0147810
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Li F;Gao B;Xu W;Chen L;Xiong S
结核病（TB）是一个主要的全球健康问题。临床活动性结核病的预后取决于结核分枝杆菌 (Mtb) 与其宿主之间复杂的相互作用。近年来，自噬因其在宿主防御细胞内病原体（包括结核分枝杆菌）中的作用而受到特别关注。在本研究中，我们旨在探讨临床分离的结核分枝杆菌诱导自噬与结核病患者临床结果的关系。我们收集了 185 株 Mtb 临床分离株，并确定了这些 Mtb 分离株对巨噬细胞自噬诱导的影响。研究发现，大多数临床分离的结核分枝杆菌能够诱导巨噬细胞中自噬体的形成，但不同分离株的自噬诱导能力存在显着差异。重要的是，我们的结果显示，自噬诱导能力差的 Mtb 感染患者表现出更严重的放射学疾病范围 (p<0.001)，并且更有可能出现不利的治疗结果 (p<0.001)。结核分枝杆菌诱导的自噬程度与一些社会人口特征（例如性别、年龄和烟草消费）以及一些实验室测试（例如血红蛋白、白细胞计数和红细胞沉降率）之间没有观察到显着关联。此外，逻辑回归分析的结果表明，临床分离的结核分枝杆菌诱导自噬的缺陷是结核病晚期放射学疾病（aOR 4.710 [1.93–11.50]）和不良治疗结果（aOR 8.309 [2.22–28.97]）的独立危险因素。这些数据表明，结核分枝杆菌分离株诱导自噬的缺陷增加了结核病患者临床结局不佳的风险，检测临床分离株诱导的自噬体形成可能有助于评估结核病结局。
Tuberculosis (TB) represents a major global health problem. The prognosis of clinically active tuberculosis depends on the complex interactions between Mycobacterium tuberculosis (Mtb) and its host. In recent years, autophagy receives particular attention for its role in host defense against intracellular pathogens, including Mtb. In present study, we aim to investigate the relationship of autophagy induction by clinical isolates of Mtb with the clinical outcomes in patients with TB. We collected 185 clinical isolates of Mtb, and determined the effect of these Mtb isolates on autophagy induction in macrophages. It was found that most of clinical isolates of Mtb were able to induce autophagosome formation in macrophages, however, the autophagy-inducing ability varied significantly among different isolates. Of importance, our results revealed that patients infected by Mtb with poor autophagy-inducing ability displayed more severe radiographic extent of disease (p<0.001), and were more likely to have unfavorable treatment outcomes (p<0.001). No significant association was observed between the extent of Mtb-induced autophagy with some socio-demographic characteristics (such as gender, age and tobacco consumption), and some laboratory tests (such as hemoglobin, leukocyte count and erythrocyte sedimentation rate). Furthermore, results from logistic regression analysis demonstrated that the defect in autophagy induction by clinical isolates of Mtb was an independent risk factor for far-advanced radiographic disease (aOR 4.710 [1.93–11.50]) and unfavorable treatment outcomes (aOR 8.309 [2.22–28.97]) in TB. These data indicated that the defect in autophagy induction by Mtb isolates increased the risk of poor clinical outcomes in TB patients, and detection of clinical isolates-induced autophagosome formation might help evaluate the TB outcomes.