Cell Reports
Volume 25, Issue 1, 2 October 2018, Pages 118-129.e4
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Article
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis

https://doi.org/10.1016/j.celrep.2018.09.003Get rights and content
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Highlights

  • VSV infection via the olfactory route leads to accumulation of microglia in the OB

  • Following infection, microglia form an innate immune barrier in the OB

  • The microglia barrier prevents viral CNS penetration via the olfactory route

  • IFNAR signaling of neurons and astrocytes regulates microglia barrier formation

Summary

In sterile neuroinflammation, a pathological role is proposed for microglia, whereas in viral encephalitis, their function is not entirely clear. Many viruses exploit the odorant system and enter the CNS via the olfactory bulb (OB). Upon intranasal vesicular stomatitis virus instillation, we show an accumulation of activated microglia and monocytes in the OB. Depletion of microglia during encephalitis results in enhanced virus spread and increased lethality. Activation, proliferation, and accumulation of microglia are regulated by type I IFN receptor signaling of neurons and astrocytes, but not of microglia. Morphological analysis of myeloid cells shows that type I IFN receptor signaling of neurons has a stronger impact on the activation of myeloid cells than of astrocytes. Thus, in the infected CNS, the cross talk among neurons, astrocytes, and microglia is critical for full microglia activation and protection from lethal encephalitis.

Keywords

encephalitis
regulation of microglia activation
neurons
astrocytes
type I IFN receptor signaling

Cited by (0)

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Present address: Division of Virology, Section Viral Vaccines, Paul Ehrlich Institute, Federal Institute for Vaccines and Biomedicines, Langen, Germany

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Present address: Institute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany

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Present address: Hotchkiss Brain Institute Advanced Microscopy Platform, University of Calgary, Calgary, AB T2N 4N1, Canada

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Present address: IDEAYA Biosciences, Inc., 2200 Sand Hill Road, Suite 110, Menlo Park, CA 94025, USA

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Lead Contact