a Department of Pathology and Laboratory Medicine, McGovern Medical School , University of Texas Health Sciences Center-Houston , Houston TX.
Int Rev Immunol. 2017 Sep 3;36(5):271-286. doi: 10.1080/08830185.2017.1356924. Epub 2017 Oct 4.
Mycobacterium tuberculosis is one of the most deadly human pathogens known today in modern world, responsible for about 1.5 million deaths annually. Development of TB disease occurs only in 1 out of 10 individuals exposed to the pathogen which indicates that the competent host defense mechanisms exist in majority of the hosts to control the infection. In the last decade, autophagy has emerged as a key host immune defense mechanism against intracellular M. tuberculosis infection. Autophagy has been demonstrated not only as an effective antimicrobial mechanism for the clearance of M. tuberculosis, but the process has also been suggested to prevent excessive inflammation to avoid the adverse effects of infection on host. Nevertheless, increasing evidences also show that in order to enhance its intracellular survival, M. tuberculosis has also evolved multiple strategies to compromise the optimal functioning of host autophagic machinery. This review describes an overview of the various host signaling pathways such as pattern recognition receptors, cytokines, nutrient starvation and other cellular stress that have been implicated in induction of autophagy during M. tuberculosis infection. The review also chalk out the complex interplay of several bacterial factors of M. tuberculosis that are known to be involved in compromising autophagy mediated defense of the host. A comprehensive understanding of the interaction of bacterial and host factors at the intersections of autophagic pathways could provide integrative insights for the development of autophagy-based prophylactics and novel therapeutic interventions for TB.
结核分枝杆菌是当今现代世界已知的最致命的人类病原体之一，每年导致约 150 万人死亡。只有在接触病原体的 10 个人中，才有 1 个人会发展为结核病，这表明大多数宿主都存在有效的宿主防御机制来控制感染。在过去的十年中，自噬已成为宿主针对细胞内结核分枝杆菌感染的关键免疫防御机制。自噬不仅被证明是清除结核分枝杆菌的有效抗菌机制，而且该过程还被认为可以防止过度炎症，从而避免感染对宿主造成的不良影响。然而，越来越多的证据表明，为了增强其在细胞内的生存能力，结核分枝杆菌还进化出多种策略来损害宿主自噬机制的最佳功能。
本文概述了各种宿主信号通路，如模式识别受体、细胞因子、营养饥饿和其他细胞应激，这些信号通路已被证明在结核分枝杆菌感染期间诱导自噬。本文还阐述了结核分枝杆菌的几种细菌因子的复杂相互作用，这些因子已知会损害自噬介导的宿主防御。全面了解细菌和宿主因子在自噬途径交叉点的相互作用，可以为基于自噬的预防性治疗和结核病的新治疗干预措施的发展提供综合见解。
