Mutations in antimicrobial peptides differently affect sleep and plasticity.

Authors

Rahul Kumar, Gokul Madhav, Priyanka Balasubramanian, Ayur Tadimalla, Rhea Lakhiani, Mugdha Joshi, Vibhu Jaggi, Anushna Pal, Imroze Khan, Krishna Melnattur

Published in

PLoS genetics. Volume 22. Issue 11. Pages e1012363. Nov 13, 2026. Epub Nov 13, 2026.

Abstract

Molecules implicated in host defense can, independent of their roles as immune mediators, regulate sleep. In mammals, cytokines such as Tumor Necrosis Factor α (TNF α) and Interleukin1β (IL1β) promote sleep. In Drosophila, infection stimulates the systemic release of a battery of antimicrobial peptides (AMPs). These fly immune effectors have been understudied as sleep modulators. We obtained mutants in different AMPs and characterized their functions in sleep and plasticity. AMP mutants slept less with a longer sleep latency, and lowered arousal thresholds. Group C mutant flies, doubly mutant for the anti-fungal peptides Metchnikowin (Mtk) and Drosomycin (Drs), showed the greatest impairments. These Group C mutants also showed an exaggerated sleep rebound, sleep rebound was unaltered in other mutants. While many classes of AMPs showed sleep deficits, different sets of AMP mutants exhibited specific disruptions in socialization and rocking induced sleep. To determine whether sleep amount and sleep functions were dissociable, we evaluated memory and quantified synapse abundance. Group C mutants uniquely exhibited normal learning and memory, and lower synapse abundance, despite sleeping the least. Group C mutants are thus able to carry out some sleep functions without sleeping much. Glial knockdown of Metchnikowin and Drosomycin mimicked the sleep phenotypes of the null mutants, these genes thus act from glia. While Group C mutants retained normal cognitive function, other AMP mutants showed impairments in sleep and memory. Sleep and memory defects in these AMP mutants were reversible - enhancing sleep of Bomanin mutants pharmacologically or behaviorally improved learning and memory. Together, these data suggest that AMPs are potent sleep modulators and that different classes of AMPs differently affect sleep and sleep dependent outcomes.

PMID:
43024642
Bibliographic data and abstract were imported from PubMed on 14 Nov 2026.

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