Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA, United States; Sleep and Performance Research Center, Washington State University, Spokane, WA, United States.
Elson S. Floyd College of Medicine, Department of Biomedical Sciences, Washington State University, Spokane, WA, United States.
Brain Behav Immun. 2021 Feb;92:184-192. doi: 10.1016/j.bbi.2020.12.008. Epub 2020 Dec 9.
Fragments of the bacterial cell wall are bioactive microbial molecules that have profound effects on the function of the brain. Some of the cell wall constituents are common to both Gram-positive and Gram-negative bacteria, e.g., peptidoglycans, while other cell wall components are specific to either Gram-positive or Gram-negative microbes. Lipopolysaccharide (LPS), also called endotoxin, is found exclusively in Gram-negative bacteria, while lipoteichoic acid (LTA) is specific to Gram-positive bacteria. The effects of peptidoglycans, their fragments, and LPS are well characterized, they induce sleep, fever and anorexia. In the present study, we investigated the sleep, body temperature and food intake modulating effects of LTA. We found that intraperitoneal injection of 100 and 250 μg LTA from B. subtilis and S. aureus increases non-rapid-eye movement sleep (NREMS) in mice. The effects were dose-dependent, and the changes were accompanied by decreased motor activity and feeding as well as febrile responses. Intraperitoneal injection of 10 μg LTA induced monophasic increases in body temperature, while 100 and 250 μg LTA from B. subtilis induced initial hypothermia followed by fever. Treatment with 250 μg LTA from S. aureus elicited monophasic hypothermia. Administration of 300 μg/kg LTA from S. aureus directly into the portal vein elicited similar sleep responses in rats but did not affect body temperature. The sleep-modulating effects of LTA were similar to that of LPS in mice, although LTA appears to be less potent. These findings suggest that the role of LTA in signaling by Gram-positive bacteria in the host body is analogous to the role of LPS/endotoxin in signaling by Gram-negative microbes. LTA may play a role in the development of sickness response in clinically manifest Gram-positive bacterial infections and may contribute to sleep signaling by the commensal intestinal microbiota.
细菌细胞壁的碎片是具有生物活性的微生物分子，对大脑功能有深远的影响。一些细胞壁成分在革兰氏阳性菌和革兰氏阴性菌中都很常见，例如肽聚糖，而其他细胞壁成分则是革兰氏阳性菌或革兰氏阴性菌所特有的。脂多糖（LPS），也称为内毒素，仅存在于革兰氏阴性菌中，而脂磷壁酸（LTA）则是革兰氏阳性菌所特有的。肽聚糖、其片段和 LPS 的作用已经得到了很好的描述，它们会诱导睡眠、发热和厌食。在本研究中，我们研究了 LTA 对睡眠、体温和摄食的调节作用。我们发现，来自枯草芽孢杆菌和金黄色葡萄球菌的 100 和 250μg LTA 腹腔注射会增加小鼠的非快速眼动睡眠（NREMS）。这种作用呈剂量依赖性，变化伴随着运动活动和摄食减少以及发热反应。腹腔注射 10μg LTA 会引起体温单相升高，而 100 和 250μg 来自枯草芽孢杆菌的 LTA 会引起初始体温降低，随后发热。来自金黄色葡萄球菌的 250μg LTA 处理会引起单相体温降低。向门静脉内注射 300μg/kg 的金黄色葡萄球菌 LTA 会在大鼠中引起类似的睡眠反应，但不会影响体温。LTA 的睡眠调节作用与 LPS 在小鼠中的作用相似，尽管 LTA 的作用似乎较弱。这些发现表明，LTA 在宿主体内革兰氏阳性菌信号传递中的作用类似于 LPS/内毒素在革兰氏阴性微生物信号传递中的作用。LTA 可能在临床上表现出的革兰氏阳性细菌感染的疾病反应发展中发挥作用，并可能有助于肠道共生微生物菌群的睡眠信号传递。
