In this work, we investigated the presence and function of TRPM8, a non-selective and cold-sensitive Ca²⁺-permeable ion channel in the primary microglia cell as well as in microglia cell line BV2. We demonstrate that primary microglia as well as BV2 express TRPM8 endogenously. Both pharmacological activation or inhibition of TRPM8 causes enhanced uptake of bacterial particles at early time points of infection. In BV2, TRPM8 activation and/or LPS-signaling alters its surface expression and cytosolic ROS production. TRPM8 modulation in the absence and presence of LPS causes differential regulation of cytosolic pH and lysosomal pH. Notably, TRPM8 modulation also alters the correlation between lysosomal pH and cytosolic pH depending on TRPM8 modulation and the presence or absence of LPS. Collectively our data suggest that TRPM8 is involved in the regulation of subcellular organelle, i.e. mitochondrial and lysosomal functions. Data also suggest that primarily TRPM8 activation, but often deviation from endogenous TRPM8 function is linked with better innate immune function mediated by microglial cells. We suggest that TRPM8-mediated regulations of sub-cellular organelle functions are more context-dependent manner. Such understanding is relevant in the context of microglial cell functions and innate immunity.

在这项工作中，我们研究了原代小胶质细胞以及小胶质细胞系 BV2 中TRPM8 的存在和功能，TRPM8 是一种非选择性且冷敏感的 Ca ^{2+渗透性离子通道。}我们证明原代小胶质细胞以及 BV2 内源性表达 TRPM8。TRPM8 的药理激活或抑制都会导致感染早期细菌颗粒的摄取增加。在 BV2 中，TRPM8 激活和/或 LPS 信号传导改变其表面表达和胞质 ROS 产生。在 LPS 不存在和存在的情况下，TRPM8 的调节会导致胞质 pH 值和溶酶体 pH 值的差异调节。值得注意的是，TRPM8 调节还改变溶酶体 pH 和细胞质 p​​H 之间的相关性，具体取决于 TRPM8 调节和 LPS 的存在或不存在。总的来说，我们的数据表明 TRPM8 参与亚细胞器的调节，即线粒体和溶酶体功能。数据还表明，主要是 TRPM8 激活，但通常偏离内源性 TRPM8 功能，与小胶质细胞介导的更好的先天免疫功能有关。我们认为 TRPM8 介导的亚细胞细胞器功能的调节更加依赖于环境。这种理解与小胶质细胞功能和先天免疫相关。