Szentirmai Éva, Buckley Katelin, Kapás Levente
Elson S. Floyd College of Medicine, Department of Translational Medicine and Physiology, Washington State University, Spokane, WA, United States of America; Sleep and Performance Research Center, Washington State University, Spokane, WA, USA.
Elson S. Floyd College of Medicine, Department of Translational Medicine and Physiology, Washington State University, Spokane, WA, United States of America.
Brain Behav Immun. 2025 Jan;123:306-314. doi: 10.1016/j.bbi.2024.09.028. Epub 2024 Sep 23.
Microbial molecules translocated from the intestinal lumen into the host's internal environment play a role in various physiological functions. Previously, we identified that butyrate, a short-chain fatty acid produced by intestinal bacteria, lipoteichoic acid, a cell wall component of gram-positive bacteria, and lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, induce sleep when their naturally occurring translocation is mimicked by direct delivery into the portal vein. Our findings suggested that these microbial molecules exert their sleep-promoting effects within the hepatoportal region. In the present experiments, we tested the hypothesis that resident liver macrophages, known as Kupffer cells, play a crucial role in the LPS-responsive, sleep-promoting mechanisms within the hepatoportal region. Intraportal administration of LPS induced increased sleep and fever in control rats. Remarkably, in Kupffer cell-depleted animals, both of these responses were significantly suppressed. These findings highlight the potential role of Kupffer cells in mediating the non-rapid-eye movement sleep-promoting and febrile effects of LPS translocated from the intestinal microbiota into the portal circulation. The strategic location of Kupffer cells within the hepatoportal region, coupled with their ability to rapidly take up LPS and other microbial molecules, together with their high secretory activity of multiple signaling molecules, underlie their key role in the communication between the intestinal microbiota and the brain.
从肠腔转移至宿主内部环境的微生物分子在多种生理功能中发挥作用。此前，我们发现，肠道细菌产生的短链脂肪酸丁酸、革兰氏阳性菌的细胞壁成分脂磷壁酸以及革兰氏阴性菌的细胞壁成分脂多糖（LPS），当通过直接注入门静脉模拟其天然转移过程时会诱导睡眠。我们的研究结果表明，这些微生物分子在肝门静脉区域发挥其促睡眠作用。在本实验中，我们测试了一个假设，即驻留在肝脏的巨噬细胞（即库普弗细胞）在肝门静脉区域内对LPS产生反应的促睡眠机制中起关键作用。向门静脉内注射LPS会使对照大鼠的睡眠时间增加和体温升高。值得注意的是，在清除了库普弗细胞的动物中，这两种反应均受到显著抑制。这些发现突出了库普弗细胞在介导从肠道微生物群转移至门静脉循环的LPS的非快速眼动睡眠促进和发热效应中的潜在作用。库普弗细胞在肝门静脉区域的战略位置，加上它们快速摄取LPS和其他微生物分子的能力，以及它们对多种信号分子的高分泌活性，构成了它们在肠道微生物群与大脑之间的通信中发挥关键作用的基础。
