Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Int J Mol Sci. 2020 Aug 10;21(16):5739. doi: 10.3390/ijms21165739.
Non-typeable (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood-brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood-cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.
非定型流感嗜血杆菌（NTHI）是一种人类呼吸道病原体，导致大多数侵袭性感染。严重的侵袭性感染，如败血症和脑膜炎很少发生，但缺乏保护疫苗和 NTHI 的抗生素耐药性增加，阻碍了治疗，并强调了其作为潜在脑膜炎病原体的相关性。脑膜炎是由病原体穿过血脑屏障并侵入免疫特权的中枢神经系统（CNS）引起的。在这项研究中，我们研究了 NTHI 在脑膜炎症之前通过侵袭脉络丛（CP）细胞进入大脑的潜力，以阐明 NTHI 的病理生理机制。使用体内形成血脑脊液屏障（BCSFB）的人 CP 上皮细胞的细胞培养模型，通过免疫荧光和电子显微镜分析粘附和侵袭。NTHI 以从血面对侧的极性方式在体外侵袭 CP 细胞。此外，与囊封的 Hib 和 HiF 菌株相比，NTHI 的侵袭率增加。菌毛的出现减弱了粘附和侵袭。因此，我们的研究结果强调了 BCSFB 作为 NTHI 进入大脑的潜在入口的作用，并为 CP 在脑膜炎过程中 NTHI 入侵中枢神经系统期间的作用提供了有力证据。
