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Abstract：
Modeling human infectious diseases using the early life stages of zebrafish provides unprecedented opportunities for visualizing and studying the interaction between pathogens and phagocytic cells of the innate immune system. Intracellular pathogens use phagocytes or other host cells, like gut epithelial cells, as a replication niche. The intracellular growth of these pathogens can be counteracted by host defense mechanisms that rely on the autophagy machinery. In recent years, zebrafish embryo infection models have provided in vivo evidence for the significance of the autophagic defenses and these models are now being used to explore autophagy as a therapeutic target. In line with studies in mammalian models, research in zebrafish has shown that selective autophagy mediated by ubiquitin receptors, such as p62, is important for host resistance against several bacterial pathogens, including Shigella flexneri, Mycobacterium marinum, and Staphylococcus aureus. Furthermore, an autophagy related process, Lc3-associated phagocytosis (LAP), proved host beneficial in the case of Salmonella Typhimurium infection but host detrimental in the case of S. aureus infection, where LAP delivers the pathogen to a replication niche. These studies provide valuable information for developing novel therapeutic strategies aimed at directing the autophagy machinery towards bacterial degradation.
摘要：
使用斑马鱼的早期生命阶段对人类传染病进行建模，为可视化和研究病原体与先天免疫系统的吞噬细胞之间的相互作用提供了前所未有的机会。细胞内病原体使用吞噬细胞或其他宿主细胞，像肠道上皮细胞一样，作为复制生态位。这些病原体的细胞内生长可以通过依赖于自噬机制的宿主防御机制来抵消。近年来,斑马鱼胚胎感染模型为自噬防御的重要性提供了体内证据，这些模型现在被用于探索自噬作为治疗靶标。根据哺乳动物模型的研究，斑马鱼的研究表明，泛素受体介导的选择性自噬，例如p62，对于宿主对几种细菌病原体的抗性很重要，包括福氏志贺氏菌,marinum分枝杆菌,和金黄色葡萄球菌。此外，自噬相关的过程，Lc3相关吞噬作用（LAP），证明宿主在鼠伤寒沙门氏菌感染的情况下是有益的，但在金黄色葡萄球菌感染的情况下是有害的，其中LAP将病原体递送到复制小生境。这些研究为开发旨在将自噬机制引向细菌降解的新型治疗策略提供了有价值的信息。
