Sharma Vartika, Verma Surbhi, Seranova Elena, Sarkar Sovan, Kumar Dhiraj
Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Institute of Cancer and Genomic Sciences, Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
Front Cell Dev Biol. 2018 Nov 13;6:147. doi: 10.3389/fcell.2018.00147. eCollection 2018.
Autophagy, a cellular homeostatic process, which ensures cellular survival under various stress conditions, has catapulted to the forefront of innate defense mechanisms during intracellular infections. The ability of autophagy to tag and target intracellular pathogens toward lysosomal degradation is central to this key defense function. However, studies involving the role and regulation of autophagy during intracellular infections largely tend to ignore the housekeeping function of autophagy. A growing number of evidences now suggest that the housekeeping function of autophagy, rather than the direct pathogen degradation function, may play a decisive role to determine the outcome of infection and immunological balance. We discuss herein the studies that establish the homeostatic and anti-inflammatory function of autophagy, as well as role of bacterial effectors in modulating and coopting these functions. Given that the core autophagy machinery remains largely the same across diverse cargos, how selectivity plays out during intracellular infection remains intriguing. We explore here, the contrasting role of autophagy adaptors being both selective as well as pleotropic in functions and discuss whether E3 ligases could bring in the specificity to cargo selectivity.
自噬是一种细胞稳态过程,可确保细胞在各种应激条件下存活,在细胞内感染期间已跃居先天防御机制的前沿。自噬将细胞内病原体标记并靶向溶酶体降解的能力是这一关键防御功能的核心。然而,关于细胞内感染期间自噬的作用和调控的研究在很大程度上往往忽略了自噬的看家功能。现在越来越多的证据表明,自噬的看家功能而非直接的病原体降解功能,可能在决定感染结果和免疫平衡方面起决定性作用。我们在此讨论确立自噬的稳态和抗炎功能的研究,以及细菌效应器在调节和利用这些功能中的作用。鉴于核心自噬机制在不同的货物中基本保持不变,细胞内感染期间选择性如何发挥作用仍然很有趣。我们在此探讨自噬衔接蛋白在功能上既具有选择性又具有多效性的对比作用,并讨论E3连接酶是否能为货物选择性带来特异性。