Caenorhabditis elegans neuropeptide NLP-27 enhances neurodegeneration and paralysis in an opioid-like manner during fungal infection

The nervous system of metazoans is involved in host-pathogen interactions to control immune activation. In Caenorhabditis elegans this includes sleep induction, mediated by neuropeptide-like proteins (NLPs), which increases the chance of survival after wounding. Here we analyzed the role of NLP-27 in the infection of C. elegans with the nematode-trapping fungus Arthrobotrys flagrans. Early responses of C. elegans were the induction of paralysis (sleep), upregulation of nlp-27 and neurodegeneration of the mechanosensing PVD neurons. Deletion of nlp-27 reduced neurodegeneration during fungal attack. Induction of nlp-27 was independent of the MAP kinase PMK-1, and expression of nlp-27 in the hypodermis was sufficient to induce paralysis. NLP-27 was also upregulated in head neurons. NLP-27 contains the pentapeptide YGGYG sequence known to bind the human μ- and κ-type opioid receptors suggesting NLP-27 acts on opioid receptors. The opioid receptor antagonist naloxone shortened the paralysis time like overexpression of NLP-27.