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Updated: May 9, 2026

A Choroid Plexus Epithelial Cell-based Model of the Human Blood-Cerebrospinal Fluid Barrier to Study Bacterial Infection from the Basolateral Side
Published on: May 6, 2016
Interactions between blood-borne Streptococcus pneumoniae and the blood-brain barrier preceding meningitis
Federico Iovino1, Carlos J Orihuela, Henk E Moorlag
1Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abstract:
Streptococcus pneumoniae (the pneumococcus) is a Gram-positive bacterium and the predominant cause of bacterial meningitis. Meningitis is thought to occur as the result of pneumococci crossing the blood-brain barrier to invade the Central Nervous System (CNS); yet little is known about the steps preceding immediate disease development. To study the interactions between pneumococci and the vascular endothelium of the blood-brain barrier prior to meningitis we used an established bacteremia-derived meningitis model in combination with immunofluorescent imaging. Brain tissue of mice infected with S. pneumoniae strain TIGR4, a clinical meningitis isolate, was investigated for the location of the bacteria in relation to the brain vasculature in various compartments. We observed that S. pneumoniae adhered preferentially to the subarachnoid vessels, and subsequently, over time, reached the more internal cerebral areas including the cerebral cortex, septum, and choroid plexus. Interestingly, pneumococci were not detected in the choroid plexus till 8 hours-post infection. In contrast to the lungs, little to no leukocyte recruitment to the brain was observed over time, though Iba-1 and GFAP staining showed that microglia and astrocytes were activated as soon as 1 hour post-infection. Our results imply that i) the local immune system of the brain is activated immediately upon entry of bacteria into the bloodstream and that ii) adhesion to the blood brain barrier is spatiotemporally controlled at different sites throughout the brain. These results provide new information on these two important steps towards the development of pneumococcal meningitis.
Insights
Streptococcus pneumoniae preferentially adheres to brain vessels, leading to meningitis. The brain’s immune cells activate quickly, but bacterial spread is controlled over time.
Area of Science:
- Neuroscience
- Infectious Disease
- Microbiology
Background:
- Streptococcus pneumoniae (pneumococcus) is a leading cause of bacterial meningitis.
- The mechanism of pneumococcal invasion across the blood-brain barrier to the Central Nervous System (CNS) remains unclear.
- Understanding early bacterial interactions with the CNS vasculature is crucial for preventing meningitis.
Purpose of the Study:
- To investigate the spatiotemporal interactions between S. pneumoniae and the brain vasculature prior to meningitis development.
- To identify the initial sites of bacterial adhesion and invasion across the blood-brain barrier.
- To examine the host immune response within the brain during early pneumococcal infection.
Main Methods:
- Utilized a mouse model of bacteremia-derived meningitis.
- Employed immunofluorescent imaging to track S. pneumoniae (strain TIGR4) in brain tissue.
- Analyzed bacterial location relative to brain vasculature and assessed immune cell activation (microglia, astrocytes, leukocytes).
Main Results:
- S. pneumoniae preferentially adhered to subarachnoid vessels, later spreading to deeper brain regions like the cerebral cortex and choroid plexus.
- Bacterial presence in the choroid plexus was detected at 8 hours post-infection.
- While leukocyte recruitment to the brain was minimal, microglia and astrocytes showed activation within 1 hour post-infection.
Conclusions:
- The brain's local immune system is activated immediately following bacterial entry into the bloodstream.
- Bacterial adhesion to the blood-brain barrier occurs in a site-specific and time-dependent manner.
- These findings provide critical insights into the early stages of pneumococcal meningitis pathogenesis.
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