Ufimtseva Elena, Eremeeva Natalya, Bayborodin Sergey, Umpeleva Tatiana, Vakhrusheva Diana, Skornyakov Sergey
Laboratory of Medical Biotechnology, Research Institute of Biochemistry, Federal Research Center of Fundamental and Translational Medicine, 2 Timakova Street, 630117, Novosibirsk, Russia; Scientific Department, Ural Research Institute for Phthisiopulmonology, National Medical Research Center of Tuberculosis and Infectious Diseases of Ministry of Health of the Russian Federation, 50 XXII Partsyezda Street, 620039, Yekaterinburg, Russia.
Scientific Department, Ural Research Institute for Phthisiopulmonology, National Medical Research Center of Tuberculosis and Infectious Diseases of Ministry of Health of the Russian Federation, 50 XXII Partsyezda Street, 620039, Yekaterinburg, Russia.
Tuberculosis (Edinb). 2019 Jan;114:77-90. doi: 10.1016/j.tube.2018.12.002. Epub 2018 Dec 6.
Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells. Our data indicate that Mtb with different virulence, as single and in colonies, with or without cording morphology, are exclusively intravacuolar pathogens with intact phagosomal membranes in viable host cells of TB patients and Mtb-infected guinea pig. Mycobacteria were detected in the cytoplasm and/or damaged vacuoles only in alveolar macrophages with morphological signs of cell death after prolonged ex vivo culture, however Mtb were found inside phagosomes in viable alveolar macrophages or cells with apoptotic/necrotic morphology in the same ex vivo cell culture. The Mtb phagosomes interacted with human different endocytic pathways, but inhibited phagolysosomal biogenesis, while intracellular vesicles containing Mtb products were fused with lysosomes in the same host cells.
结核病（TB）是一种由结核分枝杆菌（Mtb）引起的危险空气传播疾病，其特征是病原体与宿主细胞（主要是肺泡巨噬细胞）之间存在紧密的相互作用。研究结核病期间Mtb在人体细胞内的存活机制对于开发结核病治疗的新策略和新药物极为重要。我们利用肺泡巨噬细胞的体外培养以及从肺结核患者切除的肺组织中获得的组织切片，来确定Mtb在宿主细胞中的独特生存方式。我们的数据表明，具有不同毒力的Mtb，无论是单个还是成菌落形式，有无索状形态，在结核病患者和感染Mtb的豚鼠的存活宿主细胞中均为仅存在于完整吞噬体膜内的空泡内病原体。仅在长时间体外培养后出现细胞死亡形态学迹象的肺泡巨噬细胞的细胞质和/或受损空泡中检测到分枝杆菌，然而，在相同的体外细胞培养中，在存活的肺泡巨噬细胞或具有凋亡/坏死形态的细胞的吞噬体内发现了Mtb。Mtb吞噬体与人类不同的内吞途径相互作用，但抑制吞噬溶酶体的生物发生，而含有Mtb产物的细胞内囊泡则与同一宿主细胞中的溶酶体融合。
