Intracisternally localized bacterial DNA containing CpG motifs induces meningitis
Intracisternally localized bacterial DNA containing CpG motifs induces meningitis
复制标题
DOI：
10.4049/jimmunol.167.8.4616
复制
发表时间：
2001-10-15
影响因子：
4.4
通讯作者：
Tarkowski, A
中科院分区：
文献类型：
--
作者：
Deng, GM;Liu, ZQ;Tarkowski, A
未甲基化的CpG基序经常在细菌DNA中发现，并且最近已显示对白细胞发挥免疫刺激作用。由于CNS中的细菌感染会导致原核DNA的局部释放，我们想研究这种事件是否可能引发脑膜炎。为此，我们向小鼠和大鼠脑池内注射细菌DNA和含有CpG基序的寡核苷酸。脑膜炎的组织学体征在12小时内明显，并持续至少14天，其特征是单核细胞Mac-3（+）细胞的流入和T淋巴细胞的缺乏。为了研究未甲基化的CpG DNA引起脑膜炎的机制，我们删除了单核细胞/巨噬细胞群体，从而消除了脑炎症。此外，使用反义技术与NF-κ B的相互作用导致促炎细胞因子产生和脑膜炎频率的下调。此外，与血管选择素表达和抑制NO合酶的特定相互作用导致脑膜炎的显着改善，总的来说表明这种情况依赖于巨噬细胞及其产物。相反，中性粒细胞、NK细胞、T/B淋巴细胞、IL-12和补体系统在含有CpG基序的细菌DNA引发的脑膜炎中没有作用。这项研究证明，含有未甲基化CpG基序的细菌DNA诱导脑膜炎，并表明这种情况是由体内激活的巨噬细胞介导的。
Unmethylated CpG motifs are frequently found in bacterial DNA, and have recently been shown to exert immunostimulatory effects on leukocytes. Since bacterial infections in the CNS will lead to local release of prokaryotic DNA, we wanted to investigate whether such an event might trigger meningitis. To that end, we have intracisternally injected mice and rats with bacterial DNA and oligonucleotides containing CpG motifs. Histopathological signs of meningitis were evident within 12 h and lasted for at least 14 days, and were characterized by an influx of monocytic, Mac-3(+) cells and by a lack of T lymphocytes. To study the mechanisms whereby unmethylated CpG DNA gives rise to meningitis, we deleted the monocyte/macrophage population leading to abrogation of brain inflammation. Also, interaction with NF-KB using antisense technology led to down-regulation of proinflammatory cytokine production and frequency of meningitis. Furthermore, specific interactions with vascular selectin expression and inhibition of NO synthase led to a significant amelioration of meningitis, altogether indicating that this condition is dependent on macrophages and their products. In contrast, neutrophils, NK cells, T/B lymphocytes, IL-12, and complement system were not instrumental in meningitis triggered by bacterial DNA containing CpG motifs. This study proves that bacterial DNA containing unmethylated CpG motifs induces meningitis, and indicates that this condition is mediated in vivo by activated macrophages.