Clinic of the Ludwig-Maximilians, Department of Neurology, University of Munich, Marchioninistr 15, Munich 81377, Germany.
Curr Top Microbiol Immunol. 2009;336:15-40. doi: 10.1007/978-3-642-00549-7_2.
Bacterial meningitis is still an important infectious disease with a high morbidity and mortality rate. Bacterial infection of the cerebrospinal fluid (CSF) space causes a powerful inflammatory reaction that is largely responsibly for meningitis-induced tissue damage and adverse outcome of the disease. In a landmark series of experiments in the mid-1980s, cell wall components including lipooligosaccharides and lipoteichoic acid were indicated to be the key bacterial elements that can trigger the host inflammatory response in the CSF. Ten years ago, the discovery of Toll-like receptor proteins (TLRs) that allow the detection of microbial components and initiate the host immune response opened up new horizons in research on the pathophysiology of meningitis. Cell culture approaches provided the first evidence for a crucial role of TLRs in sensing meningeal pathogens including Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes. Subsequently, studies in mice with single or combined deficiencies in TLRs demonstrated that TLR activation is a key event in meningeal inflammation and, even more interestingly, a pivotal factor for meningitis-associated tissue damage. A detailed understanding of the mechanisms of host-pathogen interactions in the CSF space may generate new opportunities for specific treatment strategies for bacterial meningitis.
细菌性脑膜炎仍然是一种重要的传染病，具有高发病率和死亡率。脑脊液（CSF）空间的细菌感染会引起强烈的炎症反应，这在很大程度上是导致脑膜炎引起的组织损伤和疾病不良后果的原因。在 20 世纪 80 年代中期的一系列具有里程碑意义的实验中，细胞壁成分，包括脂寡糖和脂磷壁酸，被表明是能够触发 CSF 中宿主炎症反应的关键细菌成分。十年前，发现了 Toll 样受体蛋白（TLRs），它们能够检测微生物成分并启动宿主免疫反应，为脑膜炎的病理生理学研究开辟了新的视野。细胞培养方法为 TLR 在识别包括肺炎链球菌、脑膜炎奈瑟菌、无乳链球菌和李斯特菌在内的脑膜病原体方面的关键作用提供了第一个证据。随后，对 TLR 单一或联合缺失的小鼠进行的研究表明，TLR 激活是脑膜炎症的关键事件，更有趣的是，它是与脑膜炎相关的组织损伤的关键因素。深入了解 CSF 空间中宿主-病原体相互作用的机制，可能为细菌性脑膜炎的特定治疗策略提供新的机会。
