Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis
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, w...
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2018-10-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718314189 |
id |
doaj-bbf9da8643584d2ba5d0dca8adc964b6 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chintan Chhatbar Claudia N. Detje Elena Grabski Katharina Borst Julia Spanier Luca Ghita David A. Elliott Marta Joana Costa Jordão Nora Mueller James Sutton Chittappen K. Prajeeth Viktoria Gudi Michael A. Klein Marco Prinz Frank Bradke Martin Stangel Ulrich Kalinke |
spellingShingle |
Chintan Chhatbar Claudia N. Detje Elena Grabski Katharina Borst Julia Spanier Luca Ghita David A. Elliott Marta Joana Costa Jordão Nora Mueller James Sutton Chittappen K. Prajeeth Viktoria Gudi Michael A. Klein Marco Prinz Frank Bradke Martin Stangel Ulrich Kalinke Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis Cell Reports |
author_facet |
Chintan Chhatbar Claudia N. Detje Elena Grabski Katharina Borst Julia Spanier Luca Ghita David A. Elliott Marta Joana Costa Jordão Nora Mueller James Sutton Chittappen K. Prajeeth Viktoria Gudi Michael A. Klein Marco Prinz Frank Bradke Martin Stangel Ulrich Kalinke |
author_sort |
Chintan Chhatbar |
title |
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis |
title_short |
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis |
title_full |
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis |
title_fullStr |
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis |
title_full_unstemmed |
Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral Encephalitis |
title_sort |
type i interferon receptor signaling of neurons and astrocytes regulates microglia activation during viral encephalitis |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-10-01 |
description |
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. : The mechanisms restricting viral entry into the CNS via the olfactory route were unclear. Chhatbar et al. show that intercellular communication within the olfactory bulb (OB) among neurons, astrocytes, and microglia orchestrates formation of a microglial barrier that restricts the spread of the virus into the CNS. Keywords: encephalitis, regulation of microglia activation, neurons, astrocytes, type I IFN receptor signaling |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718314189 |
work_keys_str_mv |
AT chintanchhatbar typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT claudiandetje typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT elenagrabski typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT katharinaborst typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT juliaspanier typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT lucaghita typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT davidaelliott typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT martajoanacostajordao typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT noramueller typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT jamessutton typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT chittappenkprajeeth typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT viktoriagudi typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT michaelaklein typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT marcoprinz typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT frankbradke typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT martinstangel typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis AT ulrichkalinke typeiinterferonreceptorsignalingofneuronsandastrocytesregulatesmicrogliaactivationduringviralencephalitis |
_version_ |
1726001347042476032 |
spelling |
doaj-bbf9da8643584d2ba5d0dca8adc964b62020-11-24T21:21:04ZengElsevierCell Reports2211-12472018-10-01251118129.e4Type I Interferon Receptor Signaling of Neurons and Astrocytes Regulates Microglia Activation during Viral EncephalitisChintan Chhatbar0Claudia N. Detje1Elena Grabski2Katharina Borst3Julia Spanier4Luca Ghita5David A. Elliott6Marta Joana Costa Jordão7Nora Mueller8James Sutton9Chittappen K. Prajeeth10Viktoria Gudi11Michael A. Klein12Marco Prinz13Frank Bradke14Martin Stangel15Ulrich Kalinke16Institute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyInstitute 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, GermanyAxonal Growth and Regeneration Group, German Center for Neurodegenerative Disease Research (DZNE), Bonn, GermanyInstitute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, GermanyInstitute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, GermanyNovartis Institutes for Biomedical Research, Emeryville, CA, USAClinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, GermanyClinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, GermanyInstitute for Virology and Immunobiology, University of Wuerzburg, Wuerzburg, GermanyInstitute of Neuropathology, Freiburg University Medical Centre, Freiburg, Germany; BIOSS Centre for Biological Signaling Studies, University of Freiburg, Freiburg, GermanyAxonal Growth and Regeneration Group, German Center for Neurodegenerative Disease Research (DZNE), Bonn, GermanyClinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany; Corresponding authorInstitute 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; Corresponding authorSummary: 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. : The mechanisms restricting viral entry into the CNS via the olfactory route were unclear. Chhatbar et al. show that intercellular communication within the olfactory bulb (OB) among neurons, astrocytes, and microglia orchestrates formation of a microglial barrier that restricts the spread of the virus into the CNS. Keywords: encephalitis, regulation of microglia activation, neurons, astrocytes, type I IFN receptor signalinghttp://www.sciencedirect.com/science/article/pii/S2211124718314189 |