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

Summary
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.
Unfold all
/
Fold all
More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/840543
Start date: 01-05-2019
End date: 30-04-2021
Total budget - Public funding: 184 707,84 Euro - 184 707,00 Euro
Cordis data

Original description

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.

Status

CLOSED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018