Xenophagy is a selective macroautophagic process that protects the host cytosol by entrapping and delivering microbes to a degradative compartment. Both noncanonical autophagic pathways and xenophagy are activated by microbes during infection, but the relative importance and function of these distinct processes are not clear. In this study, we used bacterial and host mutants to dissect the contribution of autophagic processes responsible for bacterial growth restriction of Listeria monocytogenes. L. monocytogenes is a facultative intracellular pathogen that escapes from phagosomes, grows in the host cytosol, and avoids autophagy by expressing three determinants of pathogenesis: two secreted phospholipases C (PLCs; PlcA and PlcB) and a surface protein (ActA). We found that shortly after phagocytosis, wild-type (WT) L. monocytogenes escaped from a noncanonical autophagic process that targets damaged vacuoles. During this process, the autophagy marker LC3 localized to single-membrane phagosomes independently of the ULK complex, which is required for initiation of macroautophagy. However, growth restriction of bacteria lacking PlcA, PlcB, and ActA required FIP200 and TBK1, both involved in the engulfment of microbes by xenophagy. Time-lapse video microscopy revealed that deposition of LC3 on L. monocytogenes-containing vacuoles via noncanonical autophagy had no apparent role in restricting bacterial growth and that, upon access to the host cytosol, WT L. monocytogenes utilized PLCs and ActA to avoid subsequent xenophagy. In conclusion, although noncanonical autophagy targets phagosomes, xenophagy was required to restrict the growth of L. monocytogenes, an intracellular pathogen that damages the entry vacuole.

中文翻译：

---

单核细胞增生李斯特菌在吞噬作用时触发非典型自噬，但避免随后的生长受限异种吞噬

异种吞噬是一种选择性的巨噬细胞自噬过程，通过截留微生物并将其运送至降解区室来保护宿主细胞质。非典型自噬途径和异种吞噬都在感染过程中被微生物激活，但是这些不同过程的相对重要性和功能尚不清楚。在这项研究中，我们使用细菌和宿主突变体剖析了导致单核细胞增多性李斯特菌细菌生长受限的自噬过程。单核细胞增生李斯特菌是一种兼性的细胞内病原体，它通过吞噬体逃逸，在宿主细胞质中生长，并通过表达三种致病因素来避免自噬：两种分泌的磷脂酶C（PLC； PlcA和PlcB）和表面蛋白（ActA）。我们发现吞噬后不久，野生型（WT）单核细胞增生李斯特菌就从针对受损液泡的非规范自噬过程中逃脱了。在此过程中，自噬标记物LC3独立于ULK复合物而定位于单膜吞噬体，这是启动巨噬细胞自噬所必需的。但是，缺乏PlcA，PlcB和ActA的细菌的生长限制需要FIP200和TBK1，它们都涉及异种吞噬微生物。延时视频显微镜显示，LC3在单核细胞增生李斯特氏菌上的沉积通过非规范性自噬产生的含液泡在限制细菌生长方面没有明显作用，并且一旦进入宿主细胞质，WT单核细胞增生李斯特菌就利用PLC和ActA避免了随后的异种吞噬。总之，尽管非典型自噬靶向吞噬体，但异种吞噬仍需限制单核细胞增生李斯特氏菌的生长，后者是一种破坏进入液泡的细胞内病原体。