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，脑膜淋巴管 (MLV) 充当直接进入颈淋巴结 (CLN) 的引流路径，用于脑脊液 (CSF) 中所含的大分子。然而，MLV 在 CNS 病毒感染期间的作用仍未得到探索。在这里，我们发现小鼠感染几种嗜神经病毒会促进 MLV 扩张，但也会导致 MLV 介导的大分子引流受损。值得注意的是，MLV 可以将病毒从 CNS 引流到 CLN。淋巴管的手术结扎或背部 MLV 的光动力消融增加了病毒感染小鼠的神经损伤和死亡率。相比之下，用血管内皮生长因子 C 预处理可促进功能性 MLV 的扩张并减轻病毒感染的影响。一起，这些数据表明功能性 MLV 有助于病毒清除，MLV 代表了病毒从 CNS 传播到 CLN 的关键路径。因此，基于 MLV 的治疗策略可能有助于减轻感染引起的神经损伤。