Department of Neurology, University Hospital, Ludwig-Maximilians-University, Munich, Germany.
Department of Internal Medicine III (Oncology), University Hospital, Ludwig-Maximilians-University, Munich, Germany.
Front Immunol. 2018 Mar 19;9:550. doi: 10.3389/fimmu.2018.00550. eCollection 2018.
Mast cells reside on and near the cerebral vasculature, the predominant site of pneumococcal entry into the central nervous system (CNS). Although mast cells have been reported to be crucial in protecting from systemic bacterial infections, their role in bacterial infections of the CNS remained elusive. Here, we assessed the role of mast cells in pneumococcal infection and . In introductory experiments using mouse bone marrow-derived mast cells (BMMC), we found that (i) BMMC degranulate and release selected cytokines upon exposure to , (ii) the response of BMMC varies between different pneumococcal serotypes and (iii) is dependent on pneumolysin. Intriguingly though, apart from a slight enhancement of cerebrospinal fluid (CSF) pleocytosis, neither two different mast cell-deficient mutant mouse strains (WBB6F1- and C57BL/6 mice) nor pharmacologic mast cell stabilization with cromoglycate had any significant impact on the disease phenotype of experimental pneumococcal meningitis. The incomplete reversal of the enhanced CSF pleocytosis by local mast cell engraftment suggests that this phenomenon is caused by other c-Kit mutation-related mechanisms than mast cell deficiency. In conclusion, our study suggests that mast cells can be activated by . However, mast cells do not play a significant role as sentinels of pneumococcal CSF invasion and initiators of innate immunity .
肥大细胞存在于脑血管上和附近,是肺炎球菌进入中枢神经系统(CNS)的主要部位。虽然已经报道肥大细胞在保护全身细菌感染方面至关重要,但它们在中枢神经系统细菌感染中的作用仍然难以捉摸。在这里,我们评估了肥大细胞在肺炎球菌感染中的作用。在使用小鼠骨髓来源的肥大细胞(BMMC)的初步实验中,我们发现:(i)BMMC 在暴露于 时脱颗粒并释放选定的细胞因子,(ii)BMMC 的反应在不同的肺炎球菌血清型之间有所不同,(iii)依赖于肺炎球菌溶血素。然而,有趣的是,除了脑脊液(CSF)白细胞增多略有增强外,两种不同的肥大细胞缺陷(WBB6F1- 和 C57BL/6 小鼠)突变小鼠株或用色甘酸钠进行药理学肥大细胞稳定化都没有对实验性肺炎球菌性脑膜炎的疾病表型产生任何显著影响。局部肥大细胞移植不完全逆转 CSF 白细胞增多,表明这种现象是由与肥大细胞缺乏相关的其他 c-Kit 突变相关机制引起的。总之,我们的研究表明,肥大细胞可以被 激活。然而,肥大细胞在肺炎球菌 CSF 入侵的哨兵和先天免疫的启动者中并没有发挥重要作用。