Innate Immunity Promotes Sleep through Epidermal Antimicrobial Peptides

Area of Science:

• Neuroscience
• Immunology
• Molecular Biology

Background:

• Wounding and infection activate innate immunity, leading to increased sleep.
• The signaling pathways connecting peripheral injury/innate immunity to sleep induction remain largely unknown.

Purpose of the Study:

• To elucidate the mechanism by which peripheral wounds signal to the nervous system to increase sleep.
• To identify key molecules and pathways involved in wound-induced sleep.

Main Methods:

• Utilized C. elegans as a model organism to study larval molting and adult epidermal injury.
• Investigated the role of NAS-38, antimicrobial peptides (AMPs), and signaling pathways (MAPK, TGF-β-SMAD, EGFR).
• Employed genetic analysis and neuronal recordings to track signaling from epidermis to sleep-active neurons (RIS).

Main Results:

• Epidermal NAS-38 activates innate immunity and AMP production, promoting sleep.
• Multiple epidermal AMPs act as somnogens, signaling to the sleep-active RIS neuron.
• Epidermal injury in adults triggers AMP production and sleep via EGFR signaling.
• Neuropeptide-like protein (NLP)-29 signals through NPR-12 to induce sleep by depolarizing RIS neurons.

Conclusions:

• Discovered a novel cross-tissue signaling mechanism where AMPs produced in response to injury promote sleep.
• This pathway enhances survival by linking innate immunity, wound healing, and protective sleep.
• The findings suggest a conserved role for AMPs in sleep regulation across species, potentially including humans.