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Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral

Chintan Chhatbar1, Claudia N Detje1, Elena Grabski1

  • 1Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.

Cell Reports
|October 4, 2018
PubMed

Insights

Microglia protect the central nervous system (CNS) during viral encephalitis by activating in response to signals from neurons and astrocytes. Their depletion increases virus spread and lethality, highlighting their crucial protective role.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • The role of microglia in sterile neuroinflammation is established, but their function in viral encephalitis remains unclear.
  • Viruses can enter the central nervous system (CNS) through the olfactory bulb (OB) via the olfactory system.
  • Vesicular stomatitis virus (VSV) is a model virus used to study viral encephalitis.

Purpose of the Study:

  • To investigate the role of microglia in viral encephalitis.
  • To elucidate the mechanisms regulating microglial activation during CNS viral infections.
  • To understand the cross-talk between different CNS cells during encephalitis.

Main Methods:

  • Intranasal VSV instillation in a mouse model.
  • Microglia depletion experiments.
  • Analysis of type I IFN receptor signaling in neurons, astrocytes, and microglia.
  • Morphological analysis of myeloid cells.

Main Results:

  • VSV infection led to the accumulation of activated microglia and monocytes in the OB.
  • Depletion of microglia resulted in increased virus spread and higher mortality rates.
  • Type I IFN receptor signaling in neurons and astrocytes, but not microglia, regulated microglial activation, proliferation, and accumulation.
  • Neuronal type I IFN receptor signaling had a greater impact on myeloid cell activation than astrocytic signaling.

Conclusions:

  • Microglia play a critical protective role in combating viral encephalitis.
  • The activation of microglia during CNS viral infections is dependent on signaling from neurons and astrocytes.
  • Intercellular communication within the CNS is vital for effective microglial response and protection against lethal encephalitis.
Keywords:
astrocytesencephalitisneuronsregulation of microglia activationtype I IFN receptor signaling

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