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.

Nature Immunology
|March 20, 2019
PubMed

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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