AbstractWounding triggers a protective innate immune response that includes the production of antimicrobial peptides and increased sleep. Little is known, however, about how peripheral wounds signal need for sleep to the nervous system. We found that during C. elegans larval molting, a tolloid/BMP-1-like protein promotes sleep through an epidermal innate immune pathway and the expression of more than a dozen antimicrobial peptide (AMP) genes. In the adult, epidermal injury activates innate immunity and turns up AMP production to trigger sleep. We show for one AMP, NLP-29, that it acts through the neuropeptide receptor NPR-12 in neurons that depolarize the sleep-active RIS neuron to induce sleep. Sleep in turn increases the chance of surviving injury. Thus, we found a novel mechanism by which peripheral wounds signal to the nervous system to increase protective sleep. Such a long-range somnogen signaling function of AMPs might also boost sleep in other animals including humans.Highlights- Gain-of-function mutation in the tolloid/BMP-1-like NAS-38 protein increases sleep- NAS-38 activates innate immunity pathways to ramp up STAT-dependent antimicrobial peptide (AMP) expression- Wounding increases sleep through the innate immune response and AMPs- Antimicrobial peptides are long-range somnogens that act through neuronal neuropeptide receptors to depolarize a sleep-active neuron- Sleep increases the chance to survive injuryGraphical Abstract
Antimicrobial peptides signal need for sleep from peripheral wounds to the nervous system
