Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity
Dual-Track Clearance of Circulating Bacteria Balances Rapid Restoration of Blood Sterility with Induction of Adaptive Immunity
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DOI：
10.1016/j.chom.2016.05.023
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发表时间：
2016-07-13
影响因子：
30.3
通讯作者：
Verschoor, Admar
中科院分区：
文献类型：
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作者：
Broadley, Steven P.;Plaumann, Ann;Verschoor, Admar
有效清除菌血症可预防危及生命的疾病。血小板与血管内细菌的结合是一个涉及血小板糖蛋白GPIb和活化补体C3的细菌调理作用的过程，影响血液清除和抗感染免疫。使用活体显微镜观察感染单核细胞增生李斯特菌的小鼠的血流，我们发现细菌清除不是一个统一的过程，而是由平行的“快”和“慢”途径组成的“双轨”机制。“缓慢清除”通过时间依赖性细菌调理作用、随机血小板结合和经由免疫球蛋白超家族的补体受体CRIg捕获细菌-血小板复合物来调节。该机制使一些细菌免于通过枯否细胞清道夫受体在肝脏中“快速清除”和快速破坏，使它们可用于脾CD 8 α（+）树突状细胞的适应性免疫诱导。我们始终发现其他革兰氏+和革兰氏-细菌的广泛组的“快速”和“缓慢”清除模式。因此，双轨清除平衡了血液无菌性的快速恢复与特异性抗菌免疫的诱导。
Efficient clearance of bacteremia prevents life-threatening disease. Platelet binding to intravascular bacteria, a process involving platelet glycoprotein GPIb and bacterial opsonization with activated complement C3, influences blood clearance and anti-infective immunity. Using intravital microscopy of the bloodstream of mice infected with Listeriamonocytogenes, we show that bacterial clearance is not a uniform process but a "dual-track" mechanism consisting of parallel "fast" and "slow" pathways. "Slow clearance" is regulated by time-dependent bacterial opsonization, stochastic platelet binding, and capture of bacteria-platelet-complexes via the complement receptor of the immunoglobulin superfamily, CRIg. The mechanism spares some bacteria from "fast clearance" and rapid destruction in the liver via Kupffer cell scavenger receptors, keeping them available for adaptive immunity induction by splenic CD8 alpha(+) dendritic cells. We consistently find "fast" and "slow" clearance patterns for a broad panel of other Gram+ and Gram- bacteria. Thus, dual-track clearance balances rapid restoration of blood sterility with induction of specific antibacterial immunity.