GSE117700
The nuclear hormone receptor NHR-86 controls anti-pathogen responses in C. elegans [RNA-seq]
Germline-encoded pattern recognition receptors (e.g. Toll-like receptors) play key roles in innate immune activation. However, some metazoans, such as C. elegans, do not have canonical mechanisms of pattern recognition, yet they are able to mount anti-pathogen immune defenses. Here, we demonstrate that a nuclear hormone receptor (NHR), a ligand-gated transcription factor, functions in immune activation and pathogen defense. NHRs have expanded dramatically in C. elegans compared to other metazoans. Because NHRs often function redundantly, it has been challenging experimentally to characterize the biology of individual NHRs. Here, we use genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation to show NHR-86 is sufficient to activate protective immune defenses against the bacterial pathogen Pseudomonas aeruginosa. Interestingly, NHR-86 drives the transcription of immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and directly induces the transcription of infection response genes in a manner that confers protection from bacterial infection. Importantly, we found that nhr-86 does control immune gene expression and is necessary for host defense against a different pathogen, Enterococcus faecalis. Our findings characterize an ancient role of an NHR in innate immunity, and suggest that the expansion of the NHR protein family in C. elegans has been fueled in part by the need to activate immune defenses in response to pathogen attack. Overall design: Transcriptional profiles of C. elegans animals treated with immunostimulator molecule R24 in wild-type and nhr-86 loss of function animals