Center for Epigenetics and Metabolism, Department of Biological Chemistry, Institute for Immunology, School of Medicine, University of California, Irvine, CA 92697, USA.
Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9897-902. doi: 10.1073/pnas.1120636110. Epub 2013 May 28.
Organisms adapt to day-night cycles through highly specialized circadian machinery, whose molecular components anticipate and drive changes in organism behavior and metabolism. Although many effectors of the immune system are known to follow daily oscillations, the role of the circadian clock in the immune response to acute infections is not understood. Here we show that the circadian clock modulates the inflammatory response during acute infection with the pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). Mice infected with S. Typhimurium were colonized to higher levels and developed a higher proinflammatory response during the early rest period for mice, compared with other times of the day. We also demonstrate that a functional clock is required for optimal S. Typhimurium colonization and maximal induction of several proinflammatory genes. These findings point to a clock-regulated mechanism of activation of the immune response against an enteric pathogen and may suggest potential therapeutic strategies for chronopharmacologic interventions.
生物体通过高度专业化的生物钟机制来适应昼夜节律，其分子成分可预测并驱动生物体行为和代谢的变化。尽管免疫系统的许多效应器已知存在每日波动，但生物钟在急性感染免疫反应中的作用尚不清楚。在这里，我们表明生物钟在感染病原体沙门氏菌血清型 Typhimurium（S. Typhimurium）期间调节炎症反应。与一天中的其他时间相比，感染 S. Typhimurium 的小鼠在小鼠的早期休息时间被定植到更高水平，并产生更高的促炎反应。我们还证明，功能性时钟是 S. Typhimurium 定植和最大诱导几种促炎基因所必需的。这些发现指向针对肠道病原体的免疫反应的时钟调节激活机制，并可能为 chronopharmacologic 干预的潜在治疗策略提供依据。
