The hypervirulent Group B Streptococcus HvgA adhesin promotes central nervous system invasion through transcellular crossing of the choroid plexus.

IF 5.9 1区医学 Q1 NEUROSCIENCES Fluids and Barriers of the CNS Pub Date : 2024-08-16 DOI:10.1186/s12987-024-00564-2

Eva Aznar, Nathalie Strazielle, Lionel Costa, Claire Poyart, Asmaa Tazi, Jean-François Ghersi-Egea, Julie Guignot

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Abstract

Background: Group B Streptococcus (GBS) is the leading cause of neonatal meningitis responsible for a substantial cause of death and disability worldwide. The vast majority of GBS neonatal meningitis cases are due to the CC17 hypervirulent clone. However, the cellular and molecular pathways involved in brain invasion by GBS CC17 isolates remain largely elusive. Here, we studied the specific interaction of the CC17 clone with the choroid plexus, the main component of the blood-cerebrospinal fluid (CSF) barrier.

Methods: The interaction of GBS CC17 or non-CC17 strains with choroid plexus cells was studied using an in vivo mouse model of meningitis and in vitro models of primary and transformed rodent choroid plexus epithelial cells (CPEC and Z310). In vivo interaction of GBS with the choroid plexus was assessed by microscopy. Bacterial invasion and cell barrier penetration were examined in vitro, as well as chemokines and cytokines in response to infection.

Results: GBS CC17 was found associated with the choroid plexus of the lateral, 3rd and 4th ventricles. Infection of choroid plexus epithelial cells revealed an efficient internalization of the bacteria into the cells with GBS CC17 displaying a greater ability to invade these cells than a non-CC17 strain. Internalization of the GBS CC17 strain involved the CC17-specific HvgA adhesin and occurred via a clathrin-dependent mechanism leading to transcellular transcytosis across the choroid plexus epithelial monolayer. CPEC infection resulted in the secretion of several chemokines, including CCL2, CCL3, CCL20, CX3CL1, and the matrix metalloproteinase MMP3, as well as immune cell infiltration.

Conclusion: Our findings reveal a GBS strain-specific ability to infect the blood-CSF barrier, which appears to be an important site of bacterial entry and an active site of immune cell trafficking in response to infection.

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高病毒性 B 组链球菌 HvgA 粘附蛋白通过跨细胞穿越脉络丛促进中枢神经系统入侵。

背景：B 组链球菌（GBS）是新生儿脑膜炎的主要病因，也是全球死亡和残疾的主要原因。绝大多数 GBS 新生儿脑膜炎病例都是由 CC17 高病毒克隆引起的。然而，GBS CC17 分离株侵入大脑的细胞和分子途径在很大程度上仍然难以捉摸。在此，我们研究了 CC17 克隆与脉络丛（血-脑脊液（CSF）屏障的主要组成部分）的特异性相互作用：方法：使用脑膜炎小鼠体内模型和体外原代及转化啮齿动物脉络丛上皮细胞（CPEC 和 Z310）模型，研究了 GBS CC17 或非 CC17 菌株与脉络丛细胞的相互作用。通过显微镜评估了 GBS 与脉络丛的体内相互作用。在体外检测了细菌侵袭和细胞屏障穿透，以及对感染反应的趋化因子和细胞因子：结果：发现 GBS CC17 与侧脑室、第三脑室和第四脑室的脉络丛有关。对脉络丛上皮细胞的感染表明，GBS CC17比非CC17菌株更能将细菌有效地内化到细胞中。GBS CC17菌株的内化涉及CC17特异性HvgA粘附蛋白，并通过一种依赖于凝集素的机制发生，导致脉络丛上皮单层的跨细胞转运。CPEC感染导致多种趋化因子分泌，包括CCL2、CCL3、CCL20、CX3CL1和基质金属蛋白酶MMP3，以及免疫细胞浸润：我们的研究结果揭示了 GBS 菌株特异性感染血液-脑脊液屏障的能力，这似乎是细菌进入的一个重要部位，也是免疫细胞在应对感染时的一个活跃部位。

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来源期刊

Fluids and Barriers of the CNS Neuroscience-Developmental Neuroscience

CiteScore

10.70

自引率

8.20%

发文量

审稿时长

14 weeks

期刊介绍： "Fluids and Barriers of the CNS" is a scholarly open access journal that specializes in the intricate world of the central nervous system's fluids and barriers, which are pivotal for the health and well-being of the human body. This journal is a peer-reviewed platform that welcomes research manuscripts exploring the full spectrum of CNS fluids and barriers, with a particular focus on their roles in both health and disease. At the heart of this journal's interest is the cerebrospinal fluid (CSF), a vital fluid that circulates within the brain and spinal cord, playing a multifaceted role in the normal functioning of the brain and in various neurological conditions. The journal delves into the composition, circulation, and absorption of CSF, as well as its relationship with the parenchymal interstitial fluid and the neurovascular unit at the blood-brain barrier (BBB).