Center for Advanced Biotechnology and Medicine, Department of Pharmacology University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
BMC Neurosci. 2010 Feb 9;11:17. doi: 10.1186/1471-2202-11-17.
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.
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 kappaB (NFkappaB) 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.
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 NFkappaB Relish. These findings support a role of sleep in a recovery process and demonstrate a conserved feature of the Drosophila model of sleep.
免疫挑战会影响许多物种的行为。在哺乳动物中，这种适应性行为通常表现为睡眠增加。因此，睡眠被认为通过增强免疫功能从而克服挑战，对宿主有益。为了促进睡眠与免疫功能之间关系的遗传研究，我们研究了免疫反应对黑腹果蝇睡眠的影响。睡眠的行为特征以及先天免疫反应信号通路在果蝇中得到了很好的描述，并且在哺乳动物中高度保守。
革兰氏阴性菌感染或无菌性损伤引起的免疫反应会增加果蝇的睡眠。这种睡眠增加发生在治疗后上午的时间，其影响的幅度取决于接种或损伤的时间，即夜间治疗比白天治疗的效果更强。这种模式在持续黑暗中持续存在，表明生物钟的作用。生物钟基因周期的突变体消除了早晨观察到的睡眠增加，但在损伤或感染后立即表现出增强的睡眠。核因子 kappaB（NFkappaB）Relish 的突变体，这是先天免疫反应的核心，在白天的任何时候都不会因损伤或感染而增加睡眠。相反，它们保持正常的睡眠模式，直到死亡。在 Relish 突变体的脂肪体中表达全长 Relish 转基因可恢复免疫反应期间早晨的睡眠增加。脂肪体是果蝇中主要的免疫信号部位，在宿主防御中起着关键作用。
这些数据表明，免疫反应以生物钟为门控，以 NFkappaB Relish 为必需，增加了果蝇的睡眠。这些发现支持了睡眠在恢复过程中的作用，并证明了果蝇睡眠模型的一个保守特征。
