Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Department of Anatomy and Neuroscience, Faculty of Medicine, Nara Medical University, Shijo-cho, Kashihara, Nara 634-8521, Japan.
J Neuroimmunol. 2020 Jul 15;344:577244. doi: 10.1016/j.jneuroim.2020.577244. Epub 2020 Apr 15.
Toll-like receptor 2 (TLR2) recognizes a wide range of microbial molecules and plays critical roles in the initiation of innate immune responses. In the present study, we aimed to investigate whether the depletion of microglia and macrophages with clodronate liposomes (Clod-Lips) attenuates the activation of mouse brain circuits for TLR2-mediated inflammation and hypothermia. The peripheral administration of the TLR2 agonist zymosan induced nuclear factor-κB activation in microglia and macrophages and Fos expression in astrocytes/tanycytes and neurons in the circumventricular organs (CVOs). The depletion of microglia and macrophages with Clod-Lips markedly decreased zymosan-induced Fos expression in astrocytes/tanycytes and neurons in the CVOs. The treatment with Clod-Lips significantly attenuated zymosan-induced hypothermia. These results indicate that microglia and macrophages in the CVOs participate in the initiation and transmission of inflammatory responses after the peripheral administration of zymosan.
Toll 样受体 2（TLR2）识别广泛的微生物分子，并在先天免疫反应的启动中发挥关键作用。在本研究中，我们旨在研究是否用氯膦酸盐脂质体（Clod-Lips）耗竭小胶质细胞和巨噬细胞会减弱 TLR2 介导的炎症和体温过低激活小鼠大脑回路。外周给予 TLR2 激动剂酵母聚糖诱导小胶质细胞和巨噬细胞中核因子-κB 的激活，以及室周器官（CVOs）中的星形胶质细胞/室管膜细胞和神经元中的 Fos 表达。Clod-Lips 耗竭小胶质细胞和巨噬细胞可显著降低酵母聚糖诱导的 CVOs 中星形胶质细胞/室管膜细胞和神经元中的 Fos 表达。Clod-Lips 的治疗可显著减轻酵母聚糖诱导的体温过低。这些结果表明，CVOs 中的小胶质细胞和巨噬细胞参与了外周给予酵母聚糖后炎症反应的启动和传递。
