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Local and remote interactions between macrophages and microglia in neurological conditions
1Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
Abstract:
In the central nervous system (CNS) parenchymal macrophages are called microglial cells and have a distinct developmental origin and can self-renew. However, during pathological conditions, when the blood-brain-barrier becomes leaky, including after injury, in multiple sclerosis or with glioblastoma, monocyte-derived macrophages (MDM) infiltrate the CNS and cohabit with microglia. In neurodegenerative diseases such as Alzheimer's disease or ALS, MDM mostly do not enter the CNS, and instead microglia take several identities. In the specific case of ALS, the affected motor neurons are even surrounded locally by microglia, while along the peripheral nerves, by MDM-derived macrophages. The specific functions and interactions of these different myeloid cells are only starting to be recognized, but hold high promise for more targeted therapies.
Insights
Microglia and monocyte-derived macrophages (MDMs) are distinct myeloid cells in the central nervous system (CNS). Their roles vary in different neurological conditions, offering potential for targeted therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are the resident macrophages of the central nervous system (CNS) with unique origins and self-renewal capabilities.
- Pathological conditions like CNS injury, multiple sclerosis, and glioblastoma compromise the blood-brain barrier, allowing peripheral monocyte-derived macrophages (MDMs) to enter the CNS.
- In neurodegenerative diseases such as Alzheimer's disease and Amyotrophic Lateral Sclerosis (ALS), MDMs typically do not infiltrate the CNS, with microglia adopting diverse identities.
Purpose of the Study:
- To elucidate the distinct roles and interactions of microglial cells and monocyte-derived macrophages (MDMs) within the central nervous system (CNS).
- To highlight the differential infiltration and localization patterns of these myeloid cells in various pathological contexts, including neurodegenerative diseases and CNS injury.
- To underscore the therapeutic potential of understanding these myeloid cell dynamics for developing targeted treatments.
Main Methods:
- Comparative analysis of myeloid cell populations in different CNS conditions.
- Investigating the developmental origins and self-renewal properties of microglial cells.
- Examining the infiltration dynamics of monocyte-derived macrophages (MDMs) across the blood-brain barrier.
- Assessing the localization and functional specialization of microglia and MDMs in specific neurological diseases like ALS.
Main Results:
- Microglia are the primary myeloid cells in the CNS, capable of self-renewal.
- Monocyte-derived macrophages (MDMs) infiltrate the CNS during pathological states involving a compromised blood-brain barrier.
- In neurodegenerative diseases like ALS, microglia are found near affected motor neurons, while MDM-derived macrophages are located along peripheral nerves.
Conclusions:
- Microglia and monocyte-derived macrophages (MDMs) represent distinct myeloid cell populations within the CNS with context-dependent functions.
- The specific localization and interaction patterns of these cells in diseases like ALS are beginning to be understood.
- Targeting these distinct myeloid cell populations holds significant promise for developing novel therapeutic strategies for neurological disorders.
