Department of Neurology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, The Netherlands.
Clin Microbiol Rev. 2011 Jul;24(3):557-91. doi: 10.1128/CMR.00008-11.
Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy.
肺炎球菌性脑膜炎仍然与高死亡率和长期神经后遗症相关。最常见的感染途径是通过鼻咽部定植肺炎链球菌开始的，该细菌必须避免被黏膜捕获并在局部激活后逃避宿主免疫系统。在侵袭性疾病中，肺炎球菌上皮黏附后会发生血行入侵，并激活补体和凝血系统。炎症介质的释放有助于肺炎球菌穿过血脑屏障进入大脑，在那里细菌自由繁殖并引发循环抗原呈递细胞和常驻小胶质细胞的激活。由此产生的大量炎症导致进一步的中性粒细胞募集和炎症，导致众所周知的细菌性脑膜炎特征，包括脑脊液白细胞增多、耳蜗损伤、脑水肿、脑积水和脑血管并发症。实验动物模型继续加深我们对肺炎球菌性脑膜炎病理生理学的理解，并为新的辅助治疗和抗菌治疗提供了平台。本文讨论了肺炎球菌性脑膜炎病理生理学的最新观点，以及（辅助）治疗的潜在靶点。
