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Updated: Jul 3, 2026

Induction of Leptomeningeal Cells Modification Via Intracisternal Injection
Published on: May 7, 2020
Group B streptococcal membrane vesicles induce proinflammatory responses in neonatal meninges
Luke R Joyce1, Amanda Brady1, Sol Kim2
1Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.
Abstract:
Streptococcus agalactiae (Group B Streptococcus; GBS) is the leading cause of neonatal meningitis, resulting in morbidity and lasting neurological effects in survivors. GBS makes three unique glycolipids in their cell membrane, which we have previously shown to promote bloodstream survival and meningitis. GBS also produces membrane vesicles (MVs), but the lipid content is not known, nor is it known how glycolipids impact MV biogenesis, cargo, and function. Additionally, it is currently unknown how GBS MVs may contribute to systemic infection, meningitis, and resulting neuroinflammation. Here, using our isogenic lipid mutants in a clinically relevant sequence type 17 and capsule type III strain, we identify that the MV lipidome replicates that of the parent bacterial cell, and that MVs isolated from a glycolipid-devoid strain have an altered MV proteome. Investigating the impact of GBS MVs on brain endothelial cells in vitro, we observe significant increases in proinflammatory chemokines CXCL-1 and IL-6 from MVs isolated from WT and lipid mutant strains. Furthermore, we show that the proteins on the MV surface contribute to cytokine induction, which is dependent on Toll-like receptor 2 (TLR2)-mediated signaling. Finally, using a neonatal murine infection model, we observe significant increases in proinflammatory chemokines CXCL-1, IL-6, TNFα, and IL-1β in the murine leptomeninges and brain when GBS MVs are present in the cerebrospinal fluid. This work reveals unexplored functions of bacterial glycolipids in MV biogenesis and identifies GBS MVs as potent inflammatory molecules to the meninges and brain endothelium that may contribute significantly to meningitis disease progression.
Insights
Group B Streptococcus (GBS) membrane vesicles (MVs) replicate the parent cell
Area of Science:
- Microbiology and Immunology
- Neuroscience
- Molecular Biology
Background:
- Group B Streptococcus (GBS) is a primary cause of neonatal meningitis, leading to significant neurological damage.
- GBS produces unique cell membrane glycolipids that enhance survival and meningitis.
- The composition and function of GBS-derived membrane vesicles (MVs) in infection and neuroinflammation remain largely unknown.
Purpose of the Study:
- To investigate the lipid composition of GBS MVs and the impact of glycolipids on MV biogenesis and cargo.
- To determine the role of GBS MVs in inducing inflammation in brain endothelial cells and a neonatal murine meningitis model.
- To elucidate the molecular mechanisms by which GBS MVs contribute to meningitis and neuroinflammation.
Main Methods:
- Lipidomic analysis of GBS MVs derived from wild-type and isogenic glycolipid mutant strains.
- In vitro assays using brain endothelial cells to assess inflammatory responses to GBS MVs.
- In vivo studies in a neonatal murine model of meningitis to evaluate the effects of GBS MVs in the cerebrospinal fluid.
Main Results:
- GBS MV lipidome mirrors the parent bacterial cell; glycolipid absence alters MV proteome.
- GBS MVs induce significant increases in pro-inflammatory chemokines (CXCL-1, IL-6) in brain endothelial cells via TLR2 signaling.
- Presence of GBS MVs in cerebrospinal fluid elevates key inflammatory cytokines (CXCL-1, IL-6, TNFα, IL-1β) in the murine leptomeninges and brain.
Conclusions:
- Bacterial glycolipids play a crucial role in GBS MV biogenesis and composition.
- GBS MVs are potent inducers of neuroinflammation, acting on brain endothelium and meninges.
- GBS MVs represent a significant factor in the pathogenesis of meningitis and associated neurological sequelae.
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