CNSentinels | Spatiotemporal control of neuroinfection by meningeal macrophages

Summary
Due to the vital importance of the Central Nervous System (CNS), its infection and inflammation have to be tightly controlled. The surface of the CNS is connected to the periphery by a rich and complex tissue, the meninges. They contain a vast network of macrophages subdivided in two populations endowed with elusive functions. Using innovative depletion strategies in experimental mouse models, I discovered that meningeal macrophage populations represent the first line of protection against neuroinvasive pathogens. In their absence, specific areas in the meninges become highly infected, leading to fatal brain disease. The goal of ‘CNSentinels’ is to understand 1/the mechanisms controlling the spatiotemporal distribution of macrophage populations at the brain surface and 2/the relative contribution of the two macrophage populations in protecting the CNS against neuroinvasive pathogens. To this aim, I developed innovative strategies to visualize and manipulate meningeal macrophages in vivo that I will combine with cutting-edge gene editing techniques, in mice infected with lymphocytic choriomeningitis virus (LCMV). This pioneer work will help understand the spatial organization of the brain defence system and the molecular mechanisms involved in CNS protection, and will provide new avenues to design therapeutic strategies.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/949631
Start date: 01-05-2021
End date: 30-04-2026
Total budget - Public funding: 1 912 500,00 Euro - 1 912 500,00 Euro
Cordis data

Original description

Due to the vital importance of the Central Nervous System (CNS), its infection and inflammation have to be tightly controlled. The surface of the CNS is connected to the periphery by a rich and complex tissue, the meninges. They contain a vast network of macrophages subdivided in two populations endowed with elusive functions. Using innovative depletion strategies in experimental mouse models, I discovered that meningeal macrophage populations represent the first line of protection against neuroinvasive pathogens. In their absence, specific areas in the meninges become highly infected, leading to fatal brain disease. The goal of ‘CNSentinels’ is to understand 1/the mechanisms controlling the spatiotemporal distribution of macrophage populations at the brain surface and 2/the relative contribution of the two macrophage populations in protecting the CNS against neuroinvasive pathogens. To this aim, I developed innovative strategies to visualize and manipulate meningeal macrophages in vivo that I will combine with cutting-edge gene editing techniques, in mice infected with lymphocytic choriomeningitis virus (LCMV). This pioneer work will help understand the spatial organization of the brain defence system and the molecular mechanisms involved in CNS protection, and will provide new avenues to design therapeutic strategies.

Status

SIGNED

Call topic

ERC-2020-STG

Update Date

27-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2020
ERC-2020-STG