Alpha/Beta Interferon (IFN-α/β) Signaling in Astrocytes Mediates Protection against Viral Encephalomyelitis and Regulates IFN-γ-Dependent Responses

Journal of Virology
Mihyun Hwang, Cornelia C Bergmann

Abstract

The contribution of distinct central nervous system (CNS) resident cells to protective alpha/beta interferon (IFN-α/β) function following viral infections is poorly understood. Based on numerous immune regulatory functions of astrocytes, we evaluated the contribution of astrocyte IFN-α/β signaling toward protection against the nonlethal glia- and neuronotropic mouse hepatitis virus (MHV) strain A59. Analysis of gene expression associated with IFN-α/β function, e.g., pattern recognition receptors (PRRs) and interferon-stimulated genes (ISGs), revealed lower basal mRNA levels in brain-derived astrocytes than in microglia. Although astrocytes poorly induced Ifnβ mRNA following infection, they upregulated various mRNAs in the IFN-α/β pathway to a higher extent than microglia, supporting effective IFN-α/β responsiveness. Ablation of the IFN-α/β receptor (IFNAR) in astrocytes using mGFAPcre IFNARfl/fl mice resulted in severe encephalomyelitis and mortality, coincident with uncontrolled virus replication. Further, virus spread was not restricted to astrocytes but also affected microglia and neurons, despite increased and sustained Ifnα/β and ISG mRNA levels within the CNS. IFN-γ, a crucial mediator for MHV control, was not impaired in...Continue Reading

References

Apr 1, 1986·The Journal of Experimental Medicine·K InabaS Muramatsu
Jun 8, 2000·Immunity·M K Slifka, J L Whitton
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M T LiuT E Lane
Feb 13, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·M T LiuT E Lane
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cornelia C BergmannStephen A Stohlman
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jiehao ZhouNorman W Marten
Oct 4, 2003·Journal of Leukocyte Biology·Kate SchroderDavid A Hume
May 18, 2004·Neurochemistry International·Harold K Kimelberg
May 27, 2004·European Journal of Immunology·Salomé LeibundGut-LandmannWalter Reith
Aug 5, 2004·Annals of Neurology·Jörg KrausBritta Engelhardt
Mar 18, 2005·Annual Review of Immunology·Anthony W Segal
Sep 15, 2005·Biochemical and Biophysical Research Communications·Clive S McKimmieJohn K Fazakerley
Dec 24, 2005·Nature Reviews. Neuroscience·N Joan AbbottElisabeth Hansson
Jan 18, 2006·Nature Reviews. Microbiology·Cornelia C BergmannStephen A Stohlman
Feb 25, 2006·Cell·Shizuo AkiraOsamu Takeuchi
May 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sophie DelhayeThomas Michiels
Feb 6, 2007·Trends in Immunology·Cinthia FarinaEdgar Meinl
Apr 6, 2007·Biochimie·Sophie PaulThomas Michiels
Nov 15, 2007·Cell Cycle·Yinghua MaTimothy Vartanian
Apr 16, 2009·Clinical Microbiology Reviews·Trine H Mogensen
May 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Scott N Mueller, Rafi Ahmed
Dec 17, 2009·Acta Neuropathologica·Michael V Sofroniew, Harry V Vinters
Feb 4, 2010·The Journal of Experimental Medicine·Manira RayamajhiLaurel L Lenz
Apr 7, 2010·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Susan J Bender, Susan R Weiss
Jan 1, 2009·Journal of Innate Immunity·Stephane DaffisMichael S Diamond
Aug 6, 2010·PLoS Pathogens·Martin P Hosking, Thomas E Lane
Sep 15, 2010·The Journal of Experimental Medicine·Giorgio Trinchieri
Dec 31, 2010·Journal of Virology·Timothy W PharesCornelia C Bergmann
Jan 12, 2011·Immunology and Cell Biology·Joanna R Groom, Andrew D Luster

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Citations

May 3, 2020·British Journal of Pharmacology·Steve P H AlexanderMichael Spedding
Apr 16, 2019·Frontiers in Microbiology·Affan A SherKevin M Coombs
Mar 19, 2020·Frontiers in Veterinary Science·Daniel HerzbergHedie Bustamante
Jan 9, 2019·Frontiers in Immunology·Carine Savarin, Cornelia C Bergmann
Aug 24, 2019·Trends in Immunology·Katelynn A Milora, Glenn F Rall
Feb 7, 2021·Journal of Neurovirology·Debanjana Chakravarty, Jayasri Das Sarma
Feb 9, 2021·Reviews in the Neurosciences·Dian Eurike Septyaningtrias, Rina Susilowati
Jun 9, 2021·ACS Chemical Neuroscience·Mahdi Eskandarian BoroujeniAbbas Aliaghaei

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Methods Mentioned

BETA
reverse transcription-PCR
fluorescence-activated cell sorting
FACS
flow cytometry
ELISA
PCR
gene array
enzyme-linked immunosorbent assay

Software Mentioned

Pro Plus
Image
GraphPad
FlowJo
Microplate Manager
FACS Diva
GraphPad Prism

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