Viremia in the vertebrate host is a major determinant of arboviral reservoir competency, transmission efficiency, and disease severity. However, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, arthritogenic alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, alphavirus particles are cleared from the circulation by MARCO-expressing Kupffer cells in the liver, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the draining lymph node and liver is an important host defense mechanism as viremia and viral tissue burdens are elevated in MARCO^−/− mice and disease is more severe. In contrast to prior studies implicating a key role for lymph node macrophages in limiting viral dissemination, these findings exemplify a previously unrecognized arbovirus-scavenging role for lymphatic endothelial cells and improve our mechanistic understanding of viremia control during arthritogenic alphavirus infection.

中文翻译：

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MARCO+ 淋巴内皮细胞隔离致关节炎甲病毒以限制病毒血症和病毒传播


脊椎动物宿主中的病毒血症是虫媒病毒储存能力、传播效率和疾病严重程度的主要决定因素。然而，控制虫媒病毒血症的免疫机制尚不清楚。在这里，我们确定了清道夫受体 MARCO 在控制小鼠关节炎甲病毒感染期间的病毒血症中的关键作用。皮下接种后，致关节炎甲病毒颗粒通过淋巴液排出，并被引流淋巴结 (dLN) 中的 MARCO+ 淋巴内皮细胞 (LEC) 迅速捕获，从而限制病毒传播到血流中。甲病毒颗粒到达血流后，会被肝脏中表达 MARCO 的库普弗细胞从循环中清除，从而限制病毒血症和进一步的病毒传播。 MARCO 介导的甲病毒颗粒在引流淋巴结和肝脏中的积累是一种重要的宿主防御机制，因为 MARCO ^−/−小鼠的病毒血症和病毒组织负荷升高，并且疾病更加严重。与先前表明淋巴结巨噬细胞在限制病毒传播中发挥关键作用的研究相反，这些发现例证了以前未被认识到的淋巴内皮细胞的虫媒病毒清除作用，并提高了我们对致关节炎甲病毒感染期间病毒血症控制的机制的理解。