Abstract：
Borrelia burgdorferi is the causative agent of Lyme disease, a multisystemic disorder affecting primarily skin, joints and nervous system. Successful internalization and intracellular processing of borreliae by immune cells, like macrophages, is decisive for the outcome of a respective infection. Here, we use, for the first time, focused ion beam scanning electron microscopy tomography (FIB-SEM tomography) to visualize the interaction of borreliae with primary human macrophages with high resolution. We report that interaction between macrophages and the elongated and highly motile borreliae can lead to formation of membrane tunnels that extend deeper into the host cytoplasm than the actual phagosome, most probably as a result of partial extrication of captured borreliae. We also show that membrane tubulation at borreliae-containing phagosomes, a process suggested earlier as a mechanism leading to phagosome compaction but hard to visualize in live-cell imaging, is apparently a frequent phenomenon. Finally, we demonstrate that the endoplasmic reticulum (ER) forms multiple STIM1-positive contact sites with both membrane tunnels and phagosome tubulations, confirming the important role of the ER during uptake and intracellular processing of borreliae.
摘要：
伯氏疏螺旋体是莱姆病的病原体，一种主要影响皮肤的多系统疾病，关节和神经系统。免疫细胞成功内化和细胞内加工疏螺旋体，像巨噬细胞一样，对各自感染的结果是决定性的。这里,我们使用,第一次,聚焦离子束扫描电子显微镜断层扫描（FIB-SEM断层扫描），以高分辨率可视化疏螺旋体与原代人巨噬细胞的相互作用。我们报告说，巨噬细胞与细长且高度活动的疏螺旋体之间的相互作用可以导致膜隧道的形成，这些膜隧道比实际的吞噬体更深地延伸到宿主细胞质中，很可能是部分解救了捕获的疏螺旋体。我们还表明，在含有疏螺旋体的吞噬体，之前提出的一个过程是一种导致吞噬体压缩的机制，但在活细胞成像中很难可视化，显然是一个常见的现象。最后,我们证明内质网（ER）与膜隧道和吞噬管形成多个STIM1阳性接触位点，证实内质网在疏螺旋体的摄取和细胞内加工过程中的重要作用。
