肝脏巨噬细胞对胶囊的功能脆弱性决定了血液传播细菌的毒性。

The Tokushima journal of experimental medicine Pub Date : 2022-04-04 Epub Date: 2022-03-08 DOI:10.1084/jem.20212032
Haoran An, Chenyun Qian, Yijia Huang, Jing Li, Xianbin Tian, Jiaying Feng, Jiao Hu, Yujie Fang, Fangfang Jiao, Yuna Zeng, Xueting Huang, Xianbin Meng, Xue Liu, Xin Lin, Zhutian Zeng, Martin Guilliams, Alain Beschin, Yongwen Chen, Yuzhang Wu, Jing Wang, Marco Rinaldo Oggioni, John Leong, Jan-Willem Veening, Haiteng Deng, Rong Zhang, Hui Wang, Jiang Wu, Yan Cui, Jing-Ren Zhang
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引用次数: 0

摘要

许多胶囊细菌利用胶囊引起侵袭性疾病。然而,人们对胶囊如何在体内感染条件下增强细菌的毒力仍然知之甚少。在这里,我们展示了胶囊主要以肝脏为目标,在血液感染开始时提高细菌的存活率。在小鼠败血症模型中,胶囊能使人类病原体肺炎链球菌和大肠杆菌以胶囊血清型依赖的方式避开肝脏驻留巨噬细胞 Kupffer 细胞(KCs)的识别。与 KCs 有效捕获无囊细菌相反,被包裹的细菌部分(低毒性类型)或完全(高毒性类型)对 KCs "不起作用"。我们最终确定了 Asialoglycoprotein 受体(ASGR)是 KCs 上第一个识别低毒性血清型-7F 和-14 肺炎球菌胶囊的已知胶囊受体。我们的数据确定了胶囊和 KCs 之间的分子相互作用是包裹细菌的命运和毒力的主要控制者,并表明这种相互作用可作为治疗败血症感染的目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria.

Many encapsulated bacteria use capsules to cause invasive diseases. However, it remains largely unknown how the capsules enhance bacterial virulence under in vivo infection conditions. Here we show that the capsules primarily target the liver to enhance bacterial survival at the onset of blood-borne infections. In a mouse sepsis model, the capsules enabled human pathogens Streptococcus pneumoniae and Escherichia coli to circumvent the recognition of liver-resident macrophage Kupffer cells (KCs) in a capsular serotype-dependent manner. In contrast to effective capture of acapsular bacteria by KCs, the encapsulated bacteria are partially (low-virulence types) or completely (high-virulence types) "untouchable" for KCs. We finally identified the asialoglycoprotein receptor (ASGR) as the first known capsule receptor on KCs to recognize the low-virulence serotype-7F and -14 pneumococcal capsules. Our data identify the molecular interplay between the capsules and KCs as a master controller of the fate and virulence of encapsulated bacteria, and suggest that the interplay is targetable for therapeutic control of septic infections.

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