Innate Immunity Promotes Sleep through Epidermal Antimicrobial Peptides

Research output: Contribution to journalResearch articleContributedpeer-review



Wounding and infection trigger a protective innate immune response that includes the production of antimicrobial peptides in the affected tissue as well as increased sleep. Little is known, however, how peripheral wounds or innate immunity signal to the nervous system to increase sleep. We found that, during C. elegans larval molting, an epidermal tolloid/bone morphogenic protein (BMP)-1-like protein called NAS-38 promotes sleep. NAS-38 is negatively regulated by its thrombospondin domain and acts through its astacin protease domain to activate p38 mitogen-activated protein (MAP)/PMK-1 kinase and transforming growth factor β (TGF-β)-SMAD/SMA-3-dependent innate immune pathways in the epidermis that cause STAT/STA-2 and SLC6 (solute carrier)/SNF-12-dependent expression of antimicrobial peptide (AMP) genes. We show that more than a dozen epidermal AMPs act as somnogens, signaling across tissues to promote sleep through the sleep-active RIS neuron. In the adult, epidermal injury activates innate immunity and turns up AMP production to trigger sleep, a process that requires epidermal growth factor receptor (EGFR) signaling that is known to promote sleep following cellular stress. We show for one AMP, neuropeptide-like protein (NLP)-29, that it acts through the neuropeptide receptor NPR-12 in locomotion-controlling neurons that are presynaptic to RIS and that depolarize this 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 cross-tissue somnogen-signaling function of AMPs might also boost sleep in other animals, including humans.


Original languageEnglish
Pages (from-to)564-577.e12
Number of pages14
JournalCurrent biology : CB
Issue number3
Publication statusPublished - 8 Feb 2021

External IDs

Scopus 85097661014
ORCID /0000-0002-7689-8617/work/142236959



  • Adenosine Monophosphate, Animals, Antimicrobial Peptides, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Epidermis, Humans, Immunity, Innate, Sleep