Department of Internal Medicine, Radboud University Nijmegen Medical Centre, and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands.
Tuberculosis (Edinb). 2012 Sep;92(5):388-96. doi: 10.1016/j.tube.2012.05.004. Epub 2012 Jun 9.
Autophagy is a vital homeostatic process triggered by starvation and other cellular stresses, in which cytoplasmatic cargo is targeted for degradation in specialized structures termed autophagosomes. Autophagy is involved in nutrient regeneration, protein and organelle degradation, but also in clearance of intracellular pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Recent studies suggest that induction of autophagy in macrophages is an effective mechanism to enhance intracellular killing of M. tuberculosis, and that the ability of the pathogen to inhibit this process is of paramount importance for its survival. Patient studies have shown genetic associations between tuberculosis and the autophagy gene IRGM, as well as with several genes indirectly involved in autophagy. In this review we will discuss the complex interplay between M. tuberculosis and autophagy, as well as the effect of polymorphisms in autophagy-related genes on susceptibility to tuberculosis.
自噬是一种由饥饿和其他细胞应激触发的重要的体内平衡过程,其中细胞质货物被靶向到称为自噬体的专门结构中进行降解。自噬参与营养物质的再生、蛋白质和细胞器的降解,但也参与清除细胞内病原体,如结核分枝杆菌,这是结核病的病原体。最近的研究表明,诱导巨噬细胞中的自噬是增强细胞内杀伤结核分枝杆菌的有效机制,而病原体抑制这一过程的能力对其生存至关重要。患者研究表明,结核病与自噬基因 IRGM 之间以及与几个间接参与自噬的基因之间存在遗传关联。在这篇综述中,我们将讨论结核分枝杆菌与自噬之间的复杂相互作用,以及自噬相关基因多态性对结核病易感性的影响。