Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFκB Relish

Abstract

Abstract Background Immune challenge impacts behavior in many species. In mammals, this adaptive behavior is often manifested as an increase in sleep. Sleep has therefore been proposed to benefit the host by enhancing immune function and thereby overcome the challenge. To facilitate genetic studies on the relationship between sleep and immune function, we characterized the effect of the immune response on sleep in Drosophila melanogaster. Behavioral features of sleep as well as the innate immune response signaling pathways are well characterized in flies and are highly conserved in mammals. Results An immune response induced by infection with Gram-negative bacteria or by aseptic injury increased sleep in flies. The increase in sleep occurred during the morning hours after treatment and the magnitude of the effect was dependent on the time-of-day of inoculation or injury such that night-time treatment had a stronger effect than that during the daytime. This pattern persisted in constant darkness, indicating a role of the circadian clock. Mutants of the circadian clock gene, period, eliminated the increase in sleep observed in the morning, but instead showed enhanced sleep immediately after injury or infection. Null mutants of the Nuclear Factor κB (NFκB) Relish, which is central to the innate immune response, do not increase sleep in response to injury or infection at any time of day. Instead, they maintain a normal sleep pattern until they die. Expression of a full-length Relish transgene in the fat bodies of Relish mutants restored the morning increase in sleep during an immune response. Fat bodies are a major site of immune signalling in flies and have a key role in host defense. Conclusions These data demonstrate that an immune response increases sleep in flies in a manner that is gated by the circadian clock and that requires the NFκB Relish. These findings support a role of sleep in a recovery process and demonstrate a conserved feature of the Drosophila model of sleep.