针对结核分枝杆菌的细胞自主效应机制。
Cell-autonomous effector mechanisms against mycobacterium tuberculosis.
作者信息
MacMicking John D
机构信息
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06510.
出版信息
Cold Spring Harb Perspect Med. 2014 Jul 31;4(10):a018507. doi: 10.1101/cshperspect.a018507.
Few pathogens run the gauntlet of sterilizing immunity like Mycobacterium tuberculosis (Mtb). This organism infects mononuclear phagocytes and is also ingested by neutrophils, both of which possess an arsenal of cell-intrinsic effector mechanisms capable of eliminating it. Here Mtb encounters acid, oxidants, nitrosylating agents, and redox congeners, often exuberantly delivered under low oxygen tension. Further pressure is applied by withholding divalent Fe²⁺, Mn²⁺, Cu²⁺, and Zn²⁺, as well as by metabolic privation in the form of carbon needed for anaplerosis and aromatic amino acids for growth. Finally, host E3 ligases ubiquinate, cationic peptides disrupt, and lysosomal enzymes digest Mtb as part of the autophagic response to this particular pathogen. It is a testament to the evolutionary fitness of Mtb that sterilization is rarely complete, although sufficient to ensure most people infected with this airborne bacterium remain disease-free.
很少有病原体能像结核分枝杆菌（Mtb）那样经受住杀菌免疫的重重考验。这种病原体感染单核吞噬细胞，也会被中性粒细胞吞噬，而这两种细胞都拥有一系列能够消灭它的细胞内固有效应机制。在这里，Mtb会遇到酸、氧化剂、亚硝化剂和氧化还原同系物，这些物质通常在低氧张力下大量释放。通过扣留二价铁离子（Fe²⁺）、锰离子（Mn²⁺）、铜离子（Cu²⁺）和锌离子（Zn²⁺），以及通过以回补反应所需的碳和生长所需的芳香族氨基酸形式进行代谢剥夺，进一步施加压力。最后，宿主E3连接酶进行泛素化，阳离子肽进行破坏，溶酶体酶将Mtb消化，作为对这种特定病原体自噬反应的一部分。尽管足以确保大多数感染这种空气传播细菌的人保持无病状态，但杀菌很少能完全彻底，这证明了Mtb的进化适应性。
Zotero 插件