Institute of Geriatrics, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.
Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, China.
Nat Neurosci. 2022 May;25(5):577-587. doi: 10.1038/s41593-022-01063-z. Epub 2022 May 6.
Recent studies have demonstrated that brain meningeal lymphatic vessels (MLVs) act as a drainage path directly into the cervical lymph nodes (CLNs) for macromolecules contained in the cerebrospinal fluid (CSF). However, the role of MLVs during CNS viral infection remains unexplored. Here, we found that infection with several neurotropic viruses in mice promotes MLV expansion but also causes impaired MLV-mediated drainage of macromolecules. Notably, MLVs could drain virus from the CNS to CLNs. Surgical ligation of the lymph vessels or photodynamic ablation of dorsal MLVs increased neurological damage and mortality of virus-infected mice. By contrast, pretreatment with vascular endothelial growth factor C promoted expansion of functional MLVs and alleviated the effects of viral infection. Together, these data indicate that functional MLVs facilitate virus clearance, and MLVs represent a critical path for virus spreading from the CNS to the CLNs. MLV-based therapeutic strategies may thus be useful for alleviating infection-induced neurological damage.
最近的研究表明，脑脑膜淋巴管（MLVs）作为一个直接引流途径，将脑脊液（CSF）中的大分子物质排入颈部淋巴结（CLNs）。然而，MLVs 在中枢神经系统病毒感染中的作用仍未被探索。在这里，我们发现几种神经嗜性病毒感染小鼠会促进 MLV 的扩张，但也会导致大分子物质经 MLV 介导的引流受损。值得注意的是，MLVs 可以将病毒从中枢神经系统引流到 CLNs。淋巴管结扎或背侧 MLVs 的光动力消融会增加病毒感染小鼠的神经损伤和死亡率。相比之下，血管内皮生长因子 C 的预处理可促进功能性 MLVs 的扩张，并减轻病毒感染的影响。总之，这些数据表明功能性 MLVs 有助于清除病毒，MLVs 是病毒从中枢神经系统传播到 CLNs 的关键途径。因此，基于 MLV 的治疗策略可能有助于缓解感染引起的神经损伤。
