Visualizing production of beta interferon by astrocytes and microglia in brain of La Crosse virus-infected mice.

2.50
Hdl Handle:
http://hdl.handle.net/10033/269695
Title:
Visualizing production of beta interferon by astrocytes and microglia in brain of La Crosse virus-infected mice.
Authors:
Kallfass, Carsten; Ackerman, Andreas; Lienenklaus, Stefan; Weiss, Siegfried; Heimrich, Bernd; Staeheli, Peter
Abstract:
Beta interferon (IFN-β) is a major component of innate immunity in mammals, but information on the in vivo source of this cytokine after pathogen infection is still scarce. To identify the cell types responsible for IFN-β production during viral encephalitis, we used reporter mice that express firefly luciferase under the control of the IFN-β promoter and stained organ sections with luciferase-specific antibodies. Numerous luciferase-positive cells were detected in regions of La Crosse virus (LACV)-infected mouse brains that contained many infected cells. Double-staining experiments with cell-type-specific markers revealed that similar numbers of astrocytes and microglia of infected brains were luciferase positive, whereas virus-infected neurons rarely contained detectable levels of luciferase. Interestingly, if a mutant LACV unable of synthesizing the IFN-antagonistic factor NSs was used for challenge, the vast majority of the IFN-β-producing cells in infected brains were astrocytes rather than microglia. Similar conclusions were reached in a second series of experiments in which conditional reporter mice expressing the luciferase reporter gene solely in defined cell types were infected with wild-type or mutant LACV. Collectively, our data suggest that glial cells rather than infected neurons represent the major source of IFN-β in LACV-infected mouse brains. They further indicate that IFN-β synthesis in astrocytes and microglia is differentially affected by the viral IFN antagonist, presumably due to differences in LACV susceptibility of these two cell types.
Affiliation:
Department of Virology, University of Freiburg, Freiburg, Germany.
Citation:
Visualizing production of beta interferon by astrocytes and microglia in brain of La Crosse virus-infected mice. 2012, 86 (20):11223-30 J. Virol.
Journal:
Journal of virology
Issue Date:
Oct-2012
URI:
http://hdl.handle.net/10033/269695
DOI:
10.1128/JVI.01093-12
PubMed ID:
22875966
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKallfass, Carstenen_GB
dc.contributor.authorAckerman, Andreasen_GB
dc.contributor.authorLienenklaus, Stefanen_GB
dc.contributor.authorWeiss, Siegfrieden_GB
dc.contributor.authorHeimrich, Bernden_GB
dc.contributor.authorStaeheli, Peteren_GB
dc.date.accessioned2013-02-18T15:35:11Z-
dc.date.available2013-02-18T15:35:11Z-
dc.date.issued2012-10-
dc.identifier.citationVisualizing production of beta interferon by astrocytes and microglia in brain of La Crosse virus-infected mice. 2012, 86 (20):11223-30 J. Virol.en_GB
dc.identifier.issn1098-5514-
dc.identifier.pmid22875966-
dc.identifier.doi10.1128/JVI.01093-12-
dc.identifier.urihttp://hdl.handle.net/10033/269695-
dc.description.abstractBeta interferon (IFN-β) is a major component of innate immunity in mammals, but information on the in vivo source of this cytokine after pathogen infection is still scarce. To identify the cell types responsible for IFN-β production during viral encephalitis, we used reporter mice that express firefly luciferase under the control of the IFN-β promoter and stained organ sections with luciferase-specific antibodies. Numerous luciferase-positive cells were detected in regions of La Crosse virus (LACV)-infected mouse brains that contained many infected cells. Double-staining experiments with cell-type-specific markers revealed that similar numbers of astrocytes and microglia of infected brains were luciferase positive, whereas virus-infected neurons rarely contained detectable levels of luciferase. Interestingly, if a mutant LACV unable of synthesizing the IFN-antagonistic factor NSs was used for challenge, the vast majority of the IFN-β-producing cells in infected brains were astrocytes rather than microglia. Similar conclusions were reached in a second series of experiments in which conditional reporter mice expressing the luciferase reporter gene solely in defined cell types were infected with wild-type or mutant LACV. Collectively, our data suggest that glial cells rather than infected neurons represent the major source of IFN-β in LACV-infected mouse brains. They further indicate that IFN-β synthesis in astrocytes and microglia is differentially affected by the viral IFN antagonist, presumably due to differences in LACV susceptibility of these two cell types.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Journal of virologyen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAstrocytesen_GB
dc.subject.meshBrainen_GB
dc.subject.meshEncephalitis, Californiaen_GB
dc.subject.meshInterferon-betaen_GB
dc.subject.meshLa Crosse virusen_GB
dc.subject.meshLuciferases, Fireflyen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshMice, Transgenicen_GB
dc.subject.meshMicrogliaen_GB
dc.subject.meshNeuronsen_GB
dc.subject.meshPromoter Regions, Geneticen_GB
dc.titleVisualizing production of beta interferon by astrocytes and microglia in brain of La Crosse virus-infected mice.en
dc.typeArticleen
dc.contributor.departmentDepartment of Virology, University of Freiburg, Freiburg, Germany.en_GB
dc.identifier.journalJournal of virologyen_GB

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