Meningitis is an inflammation of the meninges (the protectives membranes surrounding the brain), usually caused by invasion of the brain by pathogenic microorganisms. Neonatal meningitis is particularly devastating because newborns have an immature immune system and a developing brain. It is therefore associated with a high mortality rate and frequent neurological sequelae in surviving newborns.
Neonatal bacterial meningitis usually follows a bloodstream infection. However, the brain is normally protected by physiological barriers in the brain capillaries and choroid plexus that prevent toxic substances and pathogenic microorganisms present in the blood from entering the brain.
A previous study by the team showed that Group B Streptococcus, the primary cause of neonatal meningitis, is able to cross the blood-brain barrier that separates the blood from the brain parenchyma [1]. However, it was not known whether this bacterium could cross another barrier in the brain, the choroid plexuses. The choroid plexuses, which secrete cerebrospinal fluid, form a barrier between the blood and the cerebrospinal fluid.
Using a mouse model of infection and choroid plexus cells from newborn rat pups, the “Bacteria and Perinatality” team and their collaborators discovered that Group B Streptococcus is able to cross the barrier present in the choroid plexus. They then investigated how this bacterium crosses the barrier. Unlike other microorganisms that pass between the cells that form the barrier, group B streptococcus penetrates directly into the cells to pass through them. This ability is closely linked to the expression of a protein on the bacterial surface. The researchers also showed that choroid plexus cells respond to infection. This work reveals the ability of Group B Streptococcus to interact with the choroid plexus, which appears to be an important site of entry of this bacterium into the brain and an active site of immune cell trafficking in response to infection.
Figure: Section of a Group B Streptococcus-infected mouse brain showing bacteria (green) migrating from blood vessels (red) to the choroid plexus (cyan).
These studies have shown that Group B streptococci use different mechanisms to enter the brain. Thanks to these discoveries, researchers can now consider therapeutic strategies that target bacterial proteins that interact with the brain barriers. In this way, these proteins could be a promising target for the development of novel vaccines to prevent group B streptococcal meningitis
[1] Deshayes de Cambronne R, Fouet A, Picart A, Bourrel AS, Anjou C, Bouvier G, Candeias C, Bouaboud A, Costa L, Boulay AC, Cohen-Salmon M, Plu I, Rambaud C, Faurobert E, Albiges-Rizo C, Tazi A, Poyart C, Guignot J. CC17 Group B Streptococcus exploits integrins for neonatal meningitis development J Clin Invest 2021. doi: 10.1172/JCI136737.
This work was funded by the French National Research Agency (ANR). (ANR StrepB2Brain, ANR-17-CE15-0026-01).
Reference
Aznar E, Strazielle N, Costa L, Poyart C, Asmaa Tazi A, Ghersi-Egea JF, Guignot J. The hypervirulent Group B Streptococcus HvgA adhesin promotes central nervous system invasion through transcellular crossing of the choroid plexus. Fluids Barriers CNS 2024, Aug 16;21(1):66. doi: 10.1186/s12987-024-00564-2.
