In and out: Leishmania metastasis by hijacking lymphatic system and migrating immune cells.
In and out: Leishmania metastasis by hijacking lymphatic system and migrating immune cells.
复制标题
DOI：
10.3389/fcimb.2022.941860
复制
发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
淋巴系统在针对细胞内病原体的免疫反应中发挥着至关重要的作用，最近的研究已经证明了其在促进与癌细胞相关的肿瘤传播方面的作用。然而，在由利什曼原虫Viannia亚属引起的皮肤粘膜利什曼病（MCL）中，表现出感染性转移并导致严重的远处继发性病变，这些寄生虫逃逸到继发部位的途径尚未得到详细研究。我们的结果表明，当感染与炎症相关，并且由于 dsRNA 病毒内共生体 (LRV1) 的存在而加剧时，淋巴管可以作为受感染细胞从原发部位流出并定植远处器官的有效途径。我们通过使用与或不与 dsRNA 病毒内共生体相关的细胞内利什曼原虫寄生虫 Leishmania Guyanensis (Lgy) 来挑战这一假设，该寄生虫会加剧感染并导致强烈的炎症反应，并有利于感染的转移。我们通过流式细胞术、组织学分析和转移模型中的体内成像分析了可能的货物细胞和传播途径，结果表明寄生虫不仅在细胞内传播，而且还利用迁移的免疫细胞、淋巴结（LN）和淋巴管作为游离的细胞外寄生虫传播，并遵循引流和非引流淋巴结的复杂连接，最终进入血液和远处皮肤，引起新的病变。
The lymphatic system plays a crucial role in mounting immune response against intracellular pathogens, and recent studies have documented its role in facilitating tumor dissemination linked largely with cancer cells. However, in mucocutaneous leishmaniasis (MCL) caused by Leishmania Viannia subgenus showing infectious metastasis and resulting in severe distant secondary lesions, the route of escape of these parasites to secondary sites has not yet been investigated in detail. Our results demonstrated that when infection was associated with inflammation and additionally exacerbated by the presence of dsRNA viral endosymbiont (LRV1), lymphatic vessels could serve as efficient routes for infected cells to egress from the primary site and colonize distant organs. We challenged this hypothesis by using the intracellular Leishmania protozoan parasites Leishmania guyanensis (Lgy) associated with or without a dsRNA viral endosymbiont, exacerbating the infection and responsible for a strong inflammatory response, and favoring metastasis of the infection. We analyzed possible cargo cells and the routes of dissemination through flow cytometry, histological analysis, and in vivo imaging in our metastatic model to show that parasites disseminated not only intracellularly but also as free extracellular parasites using migrating immune cells, lymph nodes (LNs), and lymph vessels, and followed intricate connections of draining and non-draining lymph node to finally end up in the blood and in distant skin, causing new lesions.