Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation
Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation
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DOI：
10.1086/342845
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发表时间：
2002-09-15
影响因子：
6.4
通讯作者：
Landmann, R
中科院分区：
文献类型：
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作者：
Echchannaoui, H;Frei, K;Landmann, R
toll样受体-2 （TLR2）介导宿主对革兰氏阳性细菌壁成分的反应。在野生型（wt）和TLR2缺陷型（TLR2(-/-)）小鼠肺炎链球菌脑膜炎模型中研究了TLR2的功能。TLR2（-/-）小鼠的死亡时间明显早于wt小鼠（P < 0.02）。两种菌株血浆白细胞介素-6水平、血液和外周器官细菌数量相似。使用头孢曲松治疗，除了27%的TLR2（-/-）小鼠外，没有wt死亡（P < .04）。在感染后3小时，通过Xenogen-CCD（电荷耦合器件）相机对荧光素酶标记的肺炎链球菌进行评估，TLR2（-/-）小鼠的脑细菌负荷高于wt小鼠。24h后，TLR2（-/-）脑脊液中肿瘤坏死因子活性高于wt小鼠（P < 0.05），并与血脑屏障通透性增加有关（Evans蓝染色，P < 0.05）。总之，TLR2的缺乏与脑膜炎的早期死亡有关，这不是由于败血症，而是由于脑细菌清除减少，随后是鞘内炎症增加。
Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P < .02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P < .04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase- tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P < .05) and was related to increased blood-brain barrier permeability (Evans blue staining, P < .05). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.