pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion.
pIgR and PECAM-1 bind to pneumococcal adhesins RrgA and PspC mediating bacterial brain invasion.
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DOI：
10.1084/jem.20161668
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发表时间：
2017-06-05
期刊：
影响因子：
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通讯作者：
Henriques-Normark B
中科院分区：
文献类型：
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作者：
Iovino F;Engelen-Lee JY;Brouwer M;van de Beek D;van der Ende A;Valls Seron M;Mellroth P;Muschiol S;Bergstrand J;Widengren J;Henriques-Normark B
肺炎球菌是细菌性脑膜炎的主要原因。Iovino等人。结果表明，肺炎球菌通过与内皮受体pIgR和PECAM-1相互作用，识别细菌表面的肺炎球菌粘附素RrgA和PSPC，从而侵入大脑并通过血脑屏障。肺炎链球菌是细菌性脑膜炎的主要原因，细菌性脑膜炎是一种威胁生命的疾病，尽管使用抗生素治疗，但病死率很高。肺炎球菌通过侵入血液并穿透血脑屏障(BBB)而引起脑膜炎。用受激发射耗竭(STED)超分辨显微镜对肺炎球菌脑膜炎死亡患者的脑活检组织进行观察，发现肺炎球菌与两种BBB内皮受体：聚合免疫球蛋白受体(PIgR)和血小板内皮细胞黏附分子(PECAM-1)共存。我们发现肺炎链球菌菌毛-1的主要粘附素RrgA与这两种受体结合，而胆碱结合蛋白PSPC仅与pIgR结合，但在较低程度上只与pIgR结合。使用菌血症脑膜炎模型和突变小鼠，以及针对这两个受体的抗体，我们可以防止肺炎球菌进入大脑和脑膜炎发展。通过向抗生素(头孢曲松)治疗的小鼠添加抗体，我们进一步减少了大脑中的细菌负担。我们的数据表明，抑制pIgR和PECAM-1具有预防肺炎球菌脑膜炎的潜力。
Pneumococci are major causes of bacterial meningitis. Iovino et al. show that pneumococci invade the brain and pass the blood–brain barrier by interacting with the endothelial receptors pIgR and PECAM-1 recognizing the pneumococcal adhesin RrgA and PspC on the bacterial surface. Streptococcus pneumoniae is the main cause of bacterial meningitis, a life-threating disease with a high case fatality rate despite treatment with antibiotics. Pneumococci cause meningitis by invading the blood and penetrating the blood–brain barrier (BBB). Using stimulated emission depletion (STED) super-resolution microscopy of brain biopsies from patients who died of pneumococcal meningitis, we observe that pneumococci colocalize with the two BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1). We show that the major adhesin of the pneumococcal pilus-1, RrgA, binds both receptors, whereas the choline binding protein PspC binds, but to a lower extent, only pIgR. Using a bacteremia-derived meningitis model and mutant mice, as well as antibodies against the two receptors, we prevent pneumococcal entry into the brain and meningitis development. By adding antibodies to antibiotic (ceftriaxone)-treated mice, we further reduce the bacterial burden in the brain. Our data suggest that inhibition of pIgR and PECAM-1 has the potential to prevent pneumococcal meningitis.