a Department of Molecular Biology , Massachusetts General Hospital , Boston , Massachusetts , United States of America.
b Program in Immunology , Harvard Medical School , Boston , Massachusetts , United States of America.
Virulence. 2018 Dec 31;9(1):683-699. doi: 10.1080/21505594.2018.1438025.
The innate immune response of the nematode Caenorhabditis elegans has been extensively studied and a variety of Toll-independent immune response pathways have been identified. Surprisingly little, however, is known about how pathogens activate the C. elegans immune response. Enterococcus faecalis and Enterococcus faecium are closely related enterococcal species that exhibit significantly different levels of virulence in C. elegans infection models. Previous work has shown that activation of the C. elegans immune response by Pseudomonas aeruginosa involves P. aeruginosa-mediated host damage. Through ultrastructural imaging, we report that infection with either E. faecalis or E. faecium causes the worm intestine to become distended with proliferating bacteria in the absence of extensive morphological changes and apparent physical damage. Genetic analysis, whole-genome transcriptional profiling, and multiplexed gene expression analysis demonstrate that both enterococcal species, whether live or dead, induce a rapid and similar transcriptional defense response dependent upon previously described immune signaling pathways. The host response to E. faecium shows a stricter dependence upon stress response signaling pathways than the response to E. faecalis. Unexpectedly, we find that E. faecium is a C. elegans pathogen and that an active wild-type host defense response is required to keep an E. faecium infection at bay. These results provide new insights into the mechanisms underlying the C. elegans immune response to pathogen infection.
秀丽隐杆线虫的先天免疫反应已经得到了广泛的研究，并且已经确定了多种 Toll 非依赖的免疫反应途径。然而，人们对病原体如何激活秀丽隐杆线虫的免疫反应知之甚少。粪肠球菌和屎肠球菌是密切相关的肠球菌种，它们在秀丽隐杆线虫感染模型中表现出显著不同的毒力水平。以前的工作表明，铜绿假单胞菌激活秀丽隐杆线虫免疫反应涉及铜绿假单胞菌介导的宿主损伤。通过超微结构成像，我们报告说，感染粪肠球菌或屎肠球菌都会导致蠕虫肠道在没有广泛形态变化和明显物理损伤的情况下扩张，增殖细菌。遗传分析、全基因组转录谱分析和多重基因表达分析表明，无论是活的还是死的，这两种肠球菌都能诱导快速且相似的转录防御反应，这依赖于先前描述的免疫信号通路。与粪肠球菌相比，宿主对屎肠球菌的反应更依赖于应激反应信号通路。出乎意料的是，我们发现屎肠球菌是秀丽隐杆线虫的病原体，并且需要一个活跃的野生型宿主防御反应来抑制屎肠球菌的感染。这些结果为秀丽隐杆线虫对病原体感染的免疫反应的机制提供了新的见解。
