Essential role of choline for pneumococcal virulence in an experimental model of meningitis
Essential role of choline for pneumococcal virulence in an experimental model of meningitis
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DOI：
10.1111/j.1365-2796.2008.01930.x
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发表时间：
2008-08-01
影响因子：
11.1
通讯作者：
Tomasz, A.
中科院分区：
文献类型：
--
作者：
Gehre, F.;Leib, S. L.;Tomasz, A.
目的：本研究的目的是阐明新认识的毒力因子胆碱在脑膜炎动物模型中对肺炎链球菌发病机制的贡献。将含有胆碱的菌株D39 Cho（-）及其等基因的无胆碱衍生物D39 Cho（-）licA 64-各自表达荚膜多糖2 -以10（3）的接种量引入脑池内。CFU注入11日龄Wistar大鼠。在感染后的第一个8小时内，两种菌株都繁殖并刺激了类似的免疫应答，其涉及高水平的促炎细胞因子、基质金属蛋白酶9（MMP-9）、IL-10的表达以及白色血细胞流入CSF。脑池内接种10（7）CFU当量的含胆碱或不含胆碱的细胞壁也引起了几乎相同的免疫应答。在采样时间超过8 h时，菌株D39 Cho（-）继续复制，伴有强烈的炎症反应和强烈的粒细胞多细胞增多。感染D39 Cho（-）的动物在20 h内死亡，组织病理学显示大脑皮层和海马的脑损伤。相比之下，由无胆碱菌株D39 Cho（-）licA 64产生的初始免疫应答在前8小时后开始下降，伴随着细菌从CSF中的消除，同时在感染后8小时出现强烈的WBC应答峰值。所有动物均存活，没有证据表明脑损伤。结论：胆碱在细胞壁是必不可少的肺炎球菌保持高毒力和宿主内生存，建立肺炎球菌脑膜炎。
Objectives: The goal of the present study was to elucidate the contribution of the newly recognized virulence factor choline to the pathogenesis of Streptococcus pneumoniae in an animal model of meningitis.Results: The choline containing strain D39Cho(-) and its isogenic choline-free derivative D39Cho(-)licA64 -each expressing the capsule polysaccharide 2 - were introduced intracisternally at an inoculum size of 10(3) CFU into 11 days old Wistar rats. During the first 8 h post infection both strains multiplied and stimulated a similar immune response that involved expression of high levels of proinflammatory cytokines, the matrix metalloproteinase 9 (MMP-9), IL-10, and the influx of white blood cells into the CSF. Virtually identical immune response was also elicited by intracisternal inoculation of 10(7) CFU equivalents of either choline-containing or choline-free cell walls. At sampling times past 8 h strain D39Cho(-) continued to replicate accompanied by an intense inflammatory response and strong granulocytic pleiocytosis. Animals infected with D39Cho(-) died within 20 h and histopathology revealed brain damage in the cerebral cortex and hippocampus. In contrast, the initial immune response generated by the choline-free strain D39Cho(-)licA64 began to decline after the first 8 h accompanied by elimination of the bacteria from the CSF in parallel with a strong WBC response peaking at 8 h after infection. All animals survived and there was no evidence for brain damage.Conclusion: Choline in the cell wall is essential for pneumococci to remain highly virulent and survive within the host and establish pneumococcal meningitis.