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CSF1R antagonism limits local restimulation of antiviral CD8+ T cells during viral encephalitis

Kristen E Funk1, Robyn S Klein2,3,4

  • 1Department of Internal Medicine, Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO, 63110, USA.

Journal of Neuroinflammation
|February 2, 2019
PubMed
Abstract

Insights

Inactivating colony-stimulating factor 1 receptor (CSF1R) impairs the immune system's ability to control West Nile virus (WNV) infection. This highlights the crucial role of microglia in antiviral defense within the central nervous system (CNS).

Area of Science:

  • Neuroimmunology
  • Virology
  • Immunology

Background:

  • Microglia, the CNS's resident macrophages, are maintained by CSF1R signaling.
  • Microglial depletion via CSF1R inactivation improves cognition in neuroinflammation models but impairs viral control.
  • The mechanisms by which CSF1R signaling impacts virologic control in neurotropic infections are unclear.

Purpose of the Study:

  • To investigate the role of CSF1R signaling in myeloid cell responses during West Nile virus (WNV) infection.
  • To determine the impact of CSF1R antagonism on viral replication and immune cell function within the CNS.

Main Methods:

  • A mouse model of neurotropic WNV infection was used.
  • Pharmacological inactivation of CSF1R was achieved using PLX5622 before infection.
  • Virologic control, mortality, and immune cell phenotypes were assessed.

Main Results:

  • CSF1R antagonism led to increased susceptibility to lethal WNV infection and impaired viral control in the CNS and periphery.
  • CSF1R antagonism reduced co-stimulatory signals on antigen-presenting cells (APCs).
  • This reduction limited T cell reactivation and viral clearance in the CNS.

Conclusions:

  • CSF1R signaling is critical for APC activation and orchestrating CNS immune responses against neurotropic viral infections.
  • Microglia play a vital role in restricting viral replication and promoting antiviral T cell responses.
  • These findings are important for evaluating CSF1R antagonism as a therapeutic strategy, particularly in neurodegenerative diseases with neuroinflammation.
Keywords:
Antiviral T cellsColony-stimulating factor 1 receptorMicrogliaPLX5622Viral encephalitisWest Nile virus

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