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Updated: Jan 27, 2026

Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells
Published on: May 19, 2020
Infection drives meningeal engraftment by inflammatory monocytes that impairs CNS immunity
Rejane Rua1, Jane Y Lee1, Alexander B Silva1
1Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Tissue macrophages have an embryonic origin and can be replenished in some tissues under steady-state conditions by blood monocytes. However, little is known about the residency and properties of infiltrating monocytes after an inflammatory challenge. The meninges of the central nervous system (CNS) are populated by a dense network of macrophages that act as resident immune sentinels. Here we show that, following lymphocytic choriomeningitis virus infection, resident meningeal macrophages (MMs) acquired viral antigen and interacted directly with infiltrating cytotoxic T lymphocytes, which led to macrophage depletion. Concurrently, the meninges were infiltrated by inflammatory monocytes that engrafted the meningeal niche and remained in situ for months after viral clearance. This engraftment led to interferon-γ-dependent functional changes in the pool of MMs, including loss of bacterial and immunoregulatory sensors. Collectively, these data indicate that peripheral monocytes can engraft the meninges after an inflammatory challenge, imprinting the compartment with long-term defects in immune function.
Insights
Inflammatory monocytes infiltrate the brain meninges after viral infection, replacing resident macrophages. This engraftment causes long-term defects in immune function within the central nervous system (CNS) meningeal compartment.
Area of Science:
- Immunology
- Neuroscience
- Infectious Disease
Background:
- Tissue macrophages, including those in the central nervous system (CNS) meninges, are crucial immune sentinels.
- The behavior and long-term effects of infiltrating monocytes after CNS inflammation are not well understood.
Purpose of the Study:
- To investigate the residency, properties, and functional impact of infiltrating monocytes in the CNS meninges following viral infection.
Main Methods:
- Induction of lymphocytic choriomeningitis virus (LCMV) infection in a mouse model.
- Analysis of meningeal macrophage (MM) and infiltrating monocyte populations using advanced imaging and immunological techniques.
- Assessment of functional changes in MMs post-engraftment.
Main Results:
- Resident MMs were depleted after viral infection due to interactions with cytotoxic T lymphocytes.
- Inflammatory monocytes infiltrated the meninges and persisted for months after viral clearance.
- Engrafted MMs exhibited long-term, interferon-γ-dependent functional defects, including altered immune sensing.
Conclusions:
- Peripheral monocytes can engraft the CNS meningeal niche after inflammatory challenges.
- This engraftment leads to persistent, detrimental alterations in the immune function of the meningeal compartment.
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