Project description
Role of meningeal macrophages in the protection of the central nervous system
The meninges are the membranous coverings of the central nervous system (CNS) that provide support for the cerebral and cranial vasculature. These tissues contain a network of macrophages subdivided into two populations with poorly studied functions. Previously, the project team discovered that meningeal macrophage populations represent the first line of defence against neuropathogens. Their absence results in infection of the meninges, leading to fatal brain disease. The goal of the EU-funded CNSentinels project is to understand the mechanisms controlling the distribution of macrophage populations at the brain's surface and elucidate the role of these populations in protecting the CNS against neuroinvasive pathogens. The project will uncover the spatial organisation of the brain's defence system as well as the mechanisms involved in CNS protection.
Objective
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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Funding Scheme
ERC-STG - Starting GrantHost institution
75654 Paris
France