MacMeninges · Control of Central Nervous Sytem inflammation by meningeal macrophages, and its impairment upon aging
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-05-01 → 2021-04-30
- EU contribution
- €184,708
- Participants
- 2
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Control of Central Nervous Sytem inflammation by meningeal macrophages, and its impairment upon aging
Recent data indicate that the immune system in the central nervous system (CNS) is linked with inflammatory and neurodegenerative diseases . Due to the presence of the cranial bone, which limits tissue expansion, brain edema and CNS inflammation have to be controlled . Similar to other barrier surfaces, the surface of the CNS is connected to the periphery by layers of highly vascularized membranes, the meninges, populated by a myriad of resident immune sentinels (such as macrophages) that block threatening pathogens . Due to their strategic location at the interface between the periphery and the brain, the meninges function as the first line of protection of the CNS and represent a major site of immune cells recruitment to block further neuroinvasion . A breach in this protective system can allow the spread of neuroinvasive pathogens (e.g. HIV, Zika) with consequent CNS damage4. However, as meninges get easily inflamed and support robust inflammatory reactions, their overactivation can drive neuroinflammation in different contexts such as autoimmune diseases, migraine, stroke or microbial infections4. Waisman A, Liblau RS, Becher B. Lancet Neurol. 2015;14(9):945-955. Manglani M, McGavern DB. Curr Opin Virol. 2017;28:116-126. Mowat AM, Scott CL, Bain CC, 2017 Nat Med. 2017 Nov 7;23(11):1258-1270. Rua R, McGavern DB. Trends Mol Med. 2018.
Data: CORDIS, © European Union
Project 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.
Original text from CORDIS.
Participants
Links
- View on CORDIS
- DOI: 10.3030/840543
- http://www.ciml.univ-mrs.fr/science/lab-rejane-rua/immunosurveillance-central-nervous-system
Data: CORDIS, © European Union