Both live and dead <i>Enterococci</i> activate <i>Caenorhabditis elegans</i> host defense via immune and stress pathways

The innate immune response of the nematode <i>Caenorhabditis elegans</i> 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 <i>C. elegans</i> immune response. <i>Enterococcus faecalis</i> and <i>Enterococcus faecium</i> are closely related enterococcal species that exhibit significantly different levels of virulence in <i>C. elegans</i> infection models. Previous work has shown that activation of the <i>C. elegans</i> immune response by <i>Pseudomonas aeruginosa</i> involves <i>P. aeruginosa-</i>mediated host damage. Through ultrastructural imaging, we report that infection with either <i>E. faecalis</i> or <i>E. faecium</i> 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 <i>E. faecium</i> shows a stricter dependence upon stress response signaling pathways than the response to <i>E. faecalis</i>. Unexpectedly, we find that <i>E. faecium</i> is a <i>C. elegans</i> pathogen and that an active wild-type host defense response is required to keep an <i>E. faecium</i> infection at bay. These results provide new insights into the mechanisms underlying the <i>C. elegans</i> immune response to pathogen infection.