Streptococcus pneumoniae meningitis and the CNS barriers.
Streptococcus pneumoniae meningitis and the CNS barriers.
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DOI：
10.3389/fcimb.2022.1106596
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
肺炎链球菌（SPN）是全球范围内引起脑膜炎的重要病因，其病理生理学涉及细菌毒力因子和宿主炎症反应对大脑的损害。在大多数肺炎链球菌脑膜炎病例中，细菌从血液转移到中枢神经系统（CNS）。肺炎链球菌转移进入中枢神经系统的主要部位尚不清楚，可能的入侵途径被认为是脑或脑膜血管或脉络丛。所有途径都要求肺炎链球菌结合并穿过血管内皮屏障，随后穿过基底膜和血管周围结构，在血 - 脑脊液屏障的情况下还包括额外的上皮屏障。肺炎链球菌在中枢神经系统中的存在会引发高度炎症，导致明显的中性粒细胞浸润。中枢神经系统内被激活的中性粒细胞分泌有毒的炎症介质，对病原体和宿主都会造成损害，包括对非增殖性神经元的损害，这会导致发病率和死亡率上升。与肺炎链球菌的转移一样，在肺炎链球菌脑膜炎中，中性粒细胞向中枢神经系统的募集需要中性粒细胞从循环中穿过血管屏障进行转移，这一过程在基础条件下受到严格调控——这是中枢神经系统“免疫特化”的一个特征。因此，脑屏障在肺炎链球菌脑膜炎中至关重要，既因为未能排除细菌和维持中枢神经系统的无菌状态，也因为随后主动募集和/或未能排除循环中的白细胞。本文综述探讨了肺炎链球菌与这些屏障的相互作用、屏障炎症反应及其治疗意义。
Streptococcus pneumoniae (SPN) is a globally significant cause of meningitis, the pathophysiology of which involves damage to the brain by both bacterial virulence factors and the host inflammatory response. In most cases of SPN meningitis bacteria translocate from the blood into the central nervous system (CNS). The principal site of SPN translocation into the CNS is not known, with possible portals of entry proposed to be the cerebral or meningeal blood vessels or the choroid plexus. All require SPN to bind to and translocate across the vascular endothelial barrier, and subsequently the basement membrane and perivascular structures, including an additional epithelial barrier in the case of the blood-CSF barrier. The presence of SPN in the CNS is highly inflammatory resulting in marked neutrophilic infiltration. The secretion of toxic inflammatory mediators by activated neutrophils within the CNS damages pathogen and host alike, including the non-replicative neurons which drives morbidity and mortality. As with the translocation of SPN, the recruitment of neutrophils into the CNS in SPN meningitis necessitates the translocation of neutrophils from the circulation across the vascular barrier, a process that is tightly regulated under basal conditions – a feature of the ‘immune specialization’ of the CNS. The brain barriers are therefore central to SPN meningitis, both through a failure to exclude bacteria and maintain CNS sterility, and subsequently through the active recruitment and/or failure to exclude circulating leukocytes. The interactions of SPN with these barriers, barrier inflammatory responses, along with their therapeutic implications, are explored in this review.
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