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Control of Central Nervous Sytem inflammation by meningeal macrophages, and its impairment upon aging

Project description

The role of macrophages in CNS inflammation

The parenchyma of the central nervous system (CNS) contains membranes known as meninges, where macrophages reside. Emerging evidence indicates that these cells have the ability to detect microbes and recruit other immune cells to the CNS. The EU-funded MacMeninges project aims to study how these macrophages respond to microbial challenges and how they contribute to CNS inflammation, a potentially lethal condition. Using a combination of techniques, researchers will investigate the impact of ageing on CNS immune responses. Ultimately, the goal is to design interventions to restore meningeal immunity and treat neuroinflammation.

Objective

Immune responses within the central nervous system (CNS) can drive fatal neuroinflammation and age-related neurodegeneration as seen in the EU but are also crucial to prevent microbial spread into the CNS. It is thus important to understand and control the parameters involved in CNS inflammation. Most studies have focused on the contribution of immune cells localized within the CNS parenchyma. While searching for novel strategies to control neuroinflammation, we and others have found that the nature and activation state of immune cells at the brain surface can profoundly influence CNS inflammation. The parenchyma is enveloped by membranes referred to as the meninges that harbor a vast network of macrophages juxtaposed to blood vasculature, thus ideally positioned to detect pathogens and orchestrate immune cell recruitment into the CNS. The overarching goal of this project is to understand the role of resident meningeal macrophages in initiating and controlling CNS inflammation. To this end, I intend to study the heterogeneity of myeloid subpopulations at steady-state and their differential ability to mount an immune response following a microbial challenge. Furthermore, I will define how natural inflammatory aging impairs the induction of CNS immune responses by meningeal macrophages, and will propose strategies to restore CNS immunity at the brain borders to protect this vital organ. This will be accomplished using combinatorial approaches, including transcriptomics, flow cytometry, histo-cytometry and intravital imaging. Macrophages will be manipulated using transcranial drug delivery and transgenic mice. Sharing skills, expertise, and tools with my host institution will be a key component of this project. Understanding meningeal immunity will open avenues for the treatment of CNS inflammation and neurodegeneration, in line with the H2020 goals of promoting research excellence in the EU to deliver solutions to important societal challenges.

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution
€ 146 227,04
Address
RUE DE TOLBIAC 101
75654 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
Links
Total cost
€ 146 227,04

Participants (1)