Opposite immune responses in Caenorhabditis elegans caused by a single gene, the neuropeptide receptor gene npr-1

The nematode Caenorhabditis elegans feeds on microbes in its natural environment. Some of these microbes are pathogenic and thus harmful to the worm. To minimize fitness reductions, C. elegans has evolved various defence mechanisms including behavioural responses (i.e., avoidance behaviour). In this study, we characterized the genetic architecture of natural variation in C. elegans avoidance behaviour against the infectious stages of the Gram-positive bacterium Bacillus thuringiensis. We performed an analysis of quantitative trait loci (QTLs) using recombinant inbred lines (RILs) and introgression lines (ILs) generated from a cross of two genetically distinct C. elegans strains, N2 and CB4856. The analysis identified several QTLs that underlie variation in the behavioural response to pathogenic and non-pathogenic bacteria. One of the candidates is the npr-1 gene, which encodes a homolog of the mammalian neuropeptide receptor. Npr-1 was previously indicated to fully contribute to behavioural defence against the Gram-negative bacterium Pseudomonas aeruginosa. Surprisingly, npr-1 influences both survival and avoidance behaviour toward B. thuringiensis in exactly the opposite way than toward P. aeruginosa. We subsequently used RNA-Seq to explore in what way npr-1 differentially influences C. elegans defence responses toward these two distinct pathogen taxa. The analysis suggests that npr - 1 mediates resistance towards P. aeruginosa through the induction of oxidative stress genes and activation of GATA transcription factors, while it seems to contribute to susceptibility towards B. thuringiensis through the repression of oxidative stress genes combined with activation of Ebox transcription factors. Our findings highlight the role of npr-1 in fine-tuning nematode defence responses depending on the microbe to which C. elegans is exposed.