Division of Biological Sciences, University of California, San Diego, California, USA.
Exp Suppl. 2022;114:115-136. doi: 10.1007/978-3-030-93306-7_5.
Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology. Here we review results about microsporidia infections in C. elegans, which began with the discovery of the intestinal-infecting species Nematocida parisii. Recent findings include new species identification in the Nematocida genus, with more intestinal-infecting species, and also a species with broader tissue tropism, the epidermal and muscle-infecting species Nematocida displodere. This species has a longer polar tube infection apparatus, which may enable its wider tissue range. After invasion, multiple Nematocida species appear to fuse host cells, which likely promotes their dissemination within host organs. Localized proteomics identified Nematocida proteins that have direct contact with the C. elegans intestinal cytosol and nucleus, and many of these host-exposed proteins belong to expanded, species-specific gene families. On the host side, forward genetic screens have identified regulators of the Intracellular Pathogen Response (IPR), which is a transcriptional response induced by both microsporidia and the Orsay virus, which is also a natural, obligate intracellular pathogen of the C. elegans intestine. The IPR constitutes a novel immune/stress response that promotes resistance against microsporidia, virus, and heat shock. Overall, the Nematocida/C. elegans system has provided insights about strategies for microsporidia pathogenesis, as well as innate defense pathways against these parasites.
微孢子虫是一种了解甚少的普遍存在的真核寄生虫，完全依赖宿主进行复制。随着自然感染遗传上易于操作的透明线虫秀丽隐杆线虫的微孢子虫物种的发现，这种宿主已被用于探索微孢子虫生物学的多个领域。在这里，我们回顾了秀丽隐杆线虫中微孢子虫感染的研究结果，该研究始于发现肠道感染物种巴黎微孢子虫。最近的发现包括在巴黎微孢子虫属中鉴定出的新物种，以及更多的肠道感染物种，还有一种具有更广泛组织嗜性的物种，即表皮和肌肉感染物种迪斯科德雷微孢子虫。该物种具有更长的极管感染装置，这可能使其具有更广泛的组织范围。入侵后，多种巴黎微孢子虫似乎融合了宿主细胞，这可能促进了它们在宿主器官内的传播。局部蛋白质组学鉴定出与秀丽隐杆线虫肠道细胞质和细胞核直接接触的巴黎微孢子虫蛋白，其中许多暴露于宿主的蛋白质属于扩展的、物种特异性的基因家族。在宿主方面，正向遗传筛选鉴定出了细胞内病原体反应（IPR）的调节剂，该反应是由微孢子虫和奥赛病毒诱导的一种转录反应，奥赛病毒也是秀丽隐杆线虫肠道的一种天然、专性细胞内病原体。IPR 构成了一种新的免疫/应激反应，可促进秀丽隐杆线虫、病毒和热休克的抗性。总的来说，巴黎微孢子虫/秀丽隐杆线虫系统提供了有关微孢子虫发病机制策略的见解，以及针对这些寄生虫的先天防御途径。
