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Cell Rep. 2018 Oct 2;25(1):118-129.e4. doi: 10.1016/j.celrep.2018.09.003.

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

Author information

1
Institute 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.
2
Axonal Growth and Regeneration Group, German Center for Neurodegenerative Disease Research (DZNE), Bonn, Germany.
3
Institute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
4
Institute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, Germany.
5
Novartis Institutes for Biomedical Research, Emeryville, CA, USA.
6
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
7
Institute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, Germany.
8
Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany. Electronic address: stangel.martin@mh-hannover.de.
9
Institute 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; Center for Systems Neuroscience, Hannover, Germany. Electronic address: ulrich.kalinke@twincore.de.

Abstract

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:

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

PMID:
30282022
DOI:
10.1016/j.celrep.2018.09.003
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