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Updated: Aug 23, 2025
Isolating Central Nervous System Tissues and Associated Meninges for the Downstream Analysis of Immune cells
Published on: May 19, 2020
Meningeal macrophages protect against viral neuroinfection
Julie Rebejac1, Elisa Eme-Scolan2, Laurie Arnaud Paroutaud1
1Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France.
Abstract:
The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II- MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.
Insights
Meningeal macrophages (MMs) protect the central nervous system from viral infections. Depleting these immune cells leads to severe meningitis, highlighting their crucial role in CNS viral defense.
Area of Science:
- Neuroimmunology
- Virology
- Cellular Biology
Background:
- The central nervous system (CNS) surface is protected by meninges housing meningeal macrophages (MMs).
- MMs exhibit distinct phenotypes (MHC-II- vs. MHC-II+) that change with age and in response to stimuli.
- The role of MMs in CNS viral infections is not fully understood.
Purpose of the Study:
- To investigate the function of tissue-resident MMs in protecting the CNS against viral infections.
- To determine the impact of MM depletion or dysfunction on viral spread and disease severity.
- To explore potential therapeutic strategies targeting MMs for CNS viral diseases.
Main Methods:
- Analysis of MHC-II expression on MMs in neonatal and adult mice.
- In vivo challenge models using LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV).
- Genetic manipulation (Stat1/Ifnar deletion) and pharmacological depletion of MMs.
- Assessment of viral load, CNS infiltration, and disease outcomes.
Main Results:
- Peripheral viral infections (LCMV) caused transient meningeal infection and activation.
- Mice lacking MMs or with impaired Stat1/Ifnar signaling showed extensive viral spread into the CNS.
- Local MM depletion resulted in meningeal infection and fatal meningitis.
- Lower MHC-II+ MM numbers correlated with increased viral load.
Conclusions:
- Meningeal macrophages are critical for preventing viral entry and spread into the CNS.
- MMs act as a crucial barrier defense against viral pathogens.
- MMs represent a potential therapeutic target for managing CNS viral infections.
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