Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus
Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus
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DOI：
10.1073/pnas.1715756115
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发表时间：
2018-03-06
影响因子：
11.1
通讯作者：
Kubes, Paul
中科院分区：
文献类型：
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作者：
Bogoslowski, Ania;Butcher, Eugene C.;Kubes, Paul
金黄色葡萄球菌是一种皮肤和呼吸道定植细菌，是社区获得性皮肤感染的主要原因。这些细菌扩散到全身循环中会导致菌血症，而菌血症的死亡率很高。因此，了解防止传播的免疫屏障对于开发新的治疗方法至关重要。在这项研究中，我们证明了金黄色葡萄球菌穿过皮肤导致病原体向引流淋巴结的一些迁移，但不会进一步。虽然淋巴结中的被膜下窦(SCS)巨噬细胞对金黄色葡萄球菌的滞留很重要，但依赖补体的中性粒细胞(不依赖于SCS巨噬细胞)通过高内皮微静脉(HEV)快速募集，导致大量中性粒细胞拦截淋巴结中的细菌。外周结节地址蛋白及其两个配体L-选择素和血小板P-选择素对于通过HEV募集中性粒细胞至关重要。几乎没有中性粒细胞通过淋巴管进入淋巴结。中性粒细胞主动吞噬金黄色葡萄球菌，帮助消毒淋巴结，防止扩散到血液和其他器官。
Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and is the leading cause of community-acquired skin infections. Dissemination of these bacteria into systemic circulation causes bacteremia, which has a high mortality rate. Therefore, understanding the immunologic barriers that prevent dissemination is critical to developing novel treatments. In this study, we demonstrate that an S. aureus breach across skin leads to some migration of the pathogen to the draining lymph node, but no further. While subcapsular sinus (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid complement-dependent neutrophil recruitment (independent of the SCS macrophage) via high endothelial venules (HEVs) resulted in high numbers of neutrophils that intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together with its two ligands, L-selectin and platelet P-selectin, are critical for recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped sterilize the lymph nodes and prevent dissemination to blood and other organs.