Meningeal inflammation and arachnoid barrier breakdown in a mouse model of neonatal bacterial meningitis
5 affiliations
- 1University of Colorado Anschutz, Department of Pediatrics, Section of Developmental Biology, Aurora, CO 80045, USA; University of Colorado Anschutz, Cell Biology Stem Cells and Development Graduate Program, Aurora, CO 80045, USA
- 2University of Colorado Anschutz, Department of Immunology and Microbiology, Aurora, CO 80045, USA
- 3Howard Hughes Medical Institute, The Collective for Psychiatric Neuroengineering, Durham, NC, USA; Duke University School of Medicine, Department of Psychiatry, Durham, NC 27710, USA; North Carolina Central University, Department of Biological and Biomedical Sciences, Durham, NC 27707, USA
- 4University of Colorado Anschutz, Department of Immunology and Microbiology, Aurora, CO 80045, USA. Electronic address: [email protected]
- 5University of Colorado Anschutz, Department of Pediatrics, Section of Developmental Biology, Aurora, CO 80045, USA; University of Colorado Anschutz, Cell Biology Stem Cells and Development Graduate Program, Aurora, CO 80045, USA. Electronic address: [email protected]
Abstract
Newborns are especially susceptible to bacterial meningitis, primarily caused by Group B Streptococcus (GBS), due to incomplete maturation of immune and barrier systems. While meningitis is well known to break down the blood-brain barrier (BBB), how the meningeal arachnoid barrier, a critical component of the blood-cerebrospinal fluid barrier (B-CSFB), responds to infection is poorly understood. Using a neonatal mouse model of bacterial meningitis, we demonstrate that GBS infection significantly increases arachnoid barrier permeability, coinciding with alterations in Claudin-11 tight junction distribution and elevated meningeal production of proinflammatory cytokines (IL-6, TNF-α, CXCL1). CD206 + /Lyve1 + border-associated macrophages (BAMs) undergo significant morphological and molecular activation post-infection, but their depletion prior to GBS infection did not attenuate arachnoid barrier leakage or inflammatory cytokine levels during infection. We show that meningeal fibroblasts are a main source of proinflammatory cytokines in response to GBS infection and that exposure to the inflammatory cytokine TNF-α alone is sufficient to induce neonatal arachnoid barrier breakdown. These results support neonatal arachnoid barrier is vulnerable to cytokine-induced breakdown in bacterial infection and highlight the role of non-immune meningeal cells like fibroblasts during bacterial infection.
Related
- Development and internal validation of a nomogram for predicting bacterial meningitis in preterm infants with late-onset sepsis
- Pneumococcal meningitis secondary to chronic orbital inflammation with skull base erosion: a case report
- Second-year sentinel surveillance of bacterial meningitis in Jordan, Egypt, and Iraq: year 2 findings from the MenMap Network (2024–2025)
- Spontaneous Enterococcus faecalis Meningitis in an Elderly Patient: A Rare Cause of Community-Acquired Bacterial Meningitis
- Bacterial Meningitis Following Robot-Assisted Radical Prostatectomy After Neoadjuvant Precision Oncology-Directed Therapy: A Case Report.
BibTeX
@article{kim2026meningeal,
title = {{Meningeal inflammation and arachnoid barrier breakdown in a mouse model of neonatal bacterial meningitis}},
author = {Sol Kim and Luke R. Joyce and Amanda Brady and Brady L. Spencer and Bradley T. Pawlikowski and Julia Derk and Kelly S. Doran and Julie A. Siegenthaler},
journal = {Cell Reports},
year = {2026},
month = oct,
doi = {10.1016/j.celrep.2026.118141},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124726012209},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Meningeal inflammation and arachnoid barrier breakdown in a mouse model of neonatal bacterial meningitis
AU - Sol Kim
AU - Luke R. Joyce
AU - Amanda Brady
AU - Brady L. Spencer
AU - Bradley T. Pawlikowski
AU - Julia Derk
AU - Kelly S. Doran
AU - Julie A. Siegenthaler
PY - 2026
DA - 2026/10/01
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118141
UR - https://linkinghub.elsevier.com/retrieve/pii/S2211124726012209
AB - Newborns are especially susceptible to bacterial meningitis, primarily caused by Group B Streptococcus (GBS), due to incomplete maturation of immune and barrier systems. While meningitis is well known to break down the blood-brain barrier (BBB), how the meningeal arachnoid barrier, a critical component of the blood-cerebrospinal fluid barrier (B-CSFB), responds to infection is poorly understood. Using a neonatal mouse model of bacterial meningitis, we demonstrate that GBS infection significantly increases arachnoid barrier permeability, coinciding with alterations in Claudin-11 tight junction distribution and elevated meningeal production of proinflammatory cytokines (IL-6, TNF-α, CXCL1). CD206 + /Lyve1 + border-associated macrophages (BAMs) undergo significant morphological and molecular activation post-infection, but their depletion prior to GBS infection did not attenuate arachnoid barrier leakage or inflammatory cytokine levels during infection. We show that meningeal fibroblasts are a main source of proinflammatory cytokines in response to GBS infection and that exposure to the inflammatory cytokine TNF-α alone is sufficient to induce neonatal arachnoid barrier breakdown. These results support neonatal arachnoid barrier is vulnerable to cytokine-induced breakdown in bacterial infection and highlight the role of non-immune meningeal cells like fibroblasts during bacterial infection.
SN - 2211-1247
SN - 2639-1856
ER -