It’s that time of year again – it feels like half the people I know are ill, some forced to stay at home and “sleep it off”. It makes sense that we sleep more when we’re ill, and we know some of the molecular players involved: as early as the 1980s, studies in mammals revealed a role for cytokines, which are hormone-like signalling molecules released during illness. More recently, studies in nematode worms and fruit flies have implicated antimicrobial peptides (AMPs) – host defence peptides found across the tree of life – in sickness-induced sleep.

In a recent preprint, researchers systematically studied the role of fruit fly AMPs in baseline sleep using loss-of-function mutants. They found that several classes of AMPs regulate sleep, with AMP mutants sleeping less. The mechanisms remain unknown, but the authors provide some pointers in their discussion: “AMPs are classically thought to act as membrane disruptors, […] However, it is increasingly clear that AMPs can act on intracellular targets as well.” Might AMPs be contributing to our sleepiness when we’re ill? Seems like an area ripe for discovery…

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Mutations in antimicrobial peptides differently affect sleep and plasticity

In bioRxiv, 30 September 2025
From the group of Krishna Melnattur, Ashoka University, India.

Snippet by Katrina Woolcock

Image credit: Figure 1 from Kumar et al. cited above (CC BY-NC 4.0).