Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier
Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood-brain barrier
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DOI：
10.1084/jem.20060482
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发表时间：
2006-08-07
影响因子：
15.3
通讯作者：
Dumenil, Guillaume
中科院分区：
文献类型：
--
作者：
Mairey, Emilie;Genovesio, Auguste;Dumenil, Guillaume
脑膜炎奈瑟氏菌是一种人鼻咽部的细菌。偶尔，这种细菌会通过一种未知的机制穿过血脑屏障到达血液并引起脑膜炎。脑膜炎球菌脓毒症病例的免疫组织学研究显示，奈瑟球菌粘附仅限于位于感染器官低血流量区域的毛细血管。这项研究导致了脑膜炎球菌在血流中遇到的阻力决定其在血管中的附着部位的假设。因此，我们研究了N.在层流室中模拟血流的液体流存在下，脑膜炎病毒与内皮细胞结合。引人注目的是，报告的各种器官的平均血流量强烈抑制初始粘附。由于已知脑微循环是高度异质性的，因此使用大鼠脑的活体成像在个体血管水平上研究脑血流速度。与组织学研究一致，仅在毛细血管中观察到与脑膜炎球菌粘附相容的剪切应力水平，毛细血管表现出短暂的流量减少。流动室试验表明，在初始附着后，细菌抵抗高血液速度，甚至繁殖，形成类似于败血症病例中观察到的小菌落。这些结果表明，奈瑟氏球菌粘附和血液微循环的联合机械特性将脑膜炎球菌靶向短暂灌注不足的脑毛细血管，从而决定疾病的发展。
Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development.