Mouse model reveals changes in cell junctions and vessels bordering the CNS in response to bacterial meningitis
Bacterial meningitis is life-threatening. Caused by infection of the brain coverings (meninges) with bacteria, such as E.coli, it's especially deadly in infants. Using mice, researchers investigate how cells in the meninges respond to E.coli infection soon after birth. Upon infection, single nucleus RNA sequencing revealed macrophages, fibroblasts and endothelial cells, which line blood vessels, significantly changed their gene activity. Endothelial cells increased the activity of TLR4, a signalling protein. In mice lacking TLR4, the response to infection was weakened. Next, the team dissected different layers of the meninges – the dura (pictured, top left) and leptomeninges (top right, bottom) – to image cell junction (green, red) and blood-brain barrier proteins (pink). Infection caused proteins normally found at cell junctions in leptomeninges endothelial cells to redistribute elsewhere and leptomeninges capillaries to become disorganised and leaky. This provides insights into how the meninges blood vessel network responds to infection.
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