Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection
Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection
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DOI：
10.1038/s41467-020-18454-0
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发表时间：
2020-09-17
影响因子：
16.6
通讯作者：
Sriskandan，Shiranee
中科院分区：
文献类型：
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作者：
Siggins，Matthew K.;Lynskey，Nicola N.;Sriskandan，Shiranee
通过淋巴系统的无辅助转移是迄今为止仅归因于癌细胞的一种传播机制。在这里，我们报告说，化脓性链球菌还劫持淋巴管以逃避局部感染部位，通过连续的淋巴结和传出淋巴管进入血液。与先前报道的吞噬细胞携带细胞内病原体的机制相比，我们展示了S。化脓性杆菌在转运过程中保留在细胞外，首先是传入淋巴管，然后是传出淋巴管，携带细菌通过连续的引流淋巴结。我们确定了对细菌淋巴传播很重要的链球菌毒力机制，并表明受感染淋巴结内的转移性链球菌抵抗并颠覆吞噬细胞的清除，从而实现复制，从而引发强烈的血流感染。研究结果表明，淋巴系统既是生存环境，又是血液循环的管道。化脓性细菌，解释了隐匿性菌血症的现象。这项工作为链球菌发病机制提供了新的视角，并对免疫产生影响。
Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report thatStreptococcus pyogenesalso hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we showS. pyogenesremain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream forS. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.