Bento Carla F, Empadinhas Nuno, Mendes Vítor
1 Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge , Cambridge, United Kingdom .
DNA Cell Biol. 2015 Apr;34(4):228-42. doi: 10.1089/dna.2014.2745. Epub 2015 Jan 21.
Tuberculosis (TB), a chronic infectious disease mainly caused by the tubercle bacillus Mycobacterium tuberculosis, is one of the world's deadliest diseases that has afflicted humanity since ancient times. Although the number of people falling ill with TB each year is declining, its incidence in many developing countries is still a major cause of concern. Upon invading host cells by phagocytosis, M. tuberculosis can replicate within infected cells by arresting the maturation of the phagosome whose function is to target the pathogen for elimination. Host cells have mechanisms of controlling this evasion by inducing autophagy, an elaborate cellular process that targets bacteria for progressive elimination, decreasing bacterial loads within infected cells. In addition, autophagy activation also aids in the control of inflammation, contributing to a more efficient innate immune response against M. tuberculosis. Several innovative TB therapies have been envisaged based on autophagy manipulation, with some of them revealing high potential for future clinical trials and eventual implementation in healthcare systems. Thus, this review highlights the recent advances on the innate immune response regulation by autophagy upon M. tuberculosis infection and the promising new autophagy-based therapies for TB.
结核病(TB)是一种主要由结核杆菌结核分枝杆菌引起的慢性传染病,是自古以来困扰人类的世界上最致命的疾病之一。尽管每年患结核病的人数在下降,但在许多发展中国家,其发病率仍然是一个主要的关切问题。结核分枝杆菌通过吞噬作用侵入宿主细胞后,可通过阻止吞噬体成熟在受感染细胞内复制,而吞噬体的功能是靶向病原体以将其清除。宿主细胞具有通过诱导自噬来控制这种逃避的机制,自噬是一种精细的细胞过程,可靶向细菌进行逐步清除,减少受感染细胞内的细菌载量。此外,自噬激活还有助于控制炎症,促进针对结核分枝杆菌的更有效的先天免疫反应。基于自噬调控设想了几种创新的结核病治疗方法,其中一些显示出在未来临床试验和最终在医疗系统中实施的巨大潜力。因此,本文重点介绍了结核分枝杆菌感染后自噬对先天免疫反应调节的最新进展以及有前景的基于自噬的新型结核病治疗方法。