Li Furong, Gao Bo, Xu Wei, Chen Ling, Xiong Sidong
Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, P.R. China.
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215006, P.R. China.
PLoS One. 2016 Jan 27;11(1):e0147810. doi: 10.1371/journal.pone.0147810. eCollection 2016.
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSION/SIGNIFICANCE: 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.
结核病是一个重大的全球健康问题。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，自噬因其在宿主抵御包括Mtb在内的细胞内病原体中的作用而受到特别关注。在本研究中，我们旨在探讨Mtb临床分离株诱导的自噬与结核病患者临床结局之间的关系。
方法/主要发现：我们收集了185株Mtb临床分离株，并测定了这些Mtb分离株对巨噬细胞自噬诱导的影响。发现大多数Mtb临床分离株能够诱导巨噬细胞中自噬体的形成，然而，不同分离株之间的自噬诱导能力差异显著。重要的是，我们的结果显示，感染自噬诱导能力差的Mtb的患者，其疾病的影像学严重程度更高（p<0.001），且更有可能出现不良治疗结局（p<0.001）。未观察到Mtb诱导的自噬程度与一些社会人口学特征（如性别、年龄和吸烟情况）以及一些实验室检查（如血红蛋白、白细胞计数和红细胞沉降率）之间存在显著关联。此外，逻辑回归分析结果表明，Mtb临床分离株诱导自噬的缺陷是结核病患者影像学病情进展严重（调整后比值比4.710 [1.93 - 11.50]）和不良治疗结局（调整后比值比8.309 [2.22 - 28.97]）的独立危险因素。
结论/意义：这些数据表明，Mtb分离株诱导自噬缺陷增加了结核病患者临床结局不良的风险，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。
