Astrocytes evoke a robust IRF7-independent type I interferon response upon neurotropic viral infection.
Astrocytes
IRF7
Innate immunity
LGTV
TBEV
Type I interferon
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
22 Sep 2023
22 Sep 2023
Historique:
received:
02
05
2023
accepted:
06
09
2023
medline:
25
9
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
epublish
Résumé
Type I interferons (IFN-I) are fundamental in controlling viral infections but fatal interferonopathy is restricted in the immune-privileged central nervous system (CNS). In contrast to the well-established role of Interferon Regulatory Factor 7 (IRF7) in the regulation of IFN-I response in the periphery, little is known about the specific function in the CNS. To investigate the role for IRF7 in antiviral response during neurotropic virus infection, mice deficient for IRF3 and IRF7 were infected systemically with Langat virus (LGTV). Viral burden and IFN-I response was analyzed in the periphery and the CNS by focus formation assay, RT-PCR, immunohistochemistry and in vivo imaging. Microglia and infiltration of CNS-infiltration of immune cells were characterized by flow cytometry. Here, we demonstrate that during infection with the neurotropic Langat virus (LGTV), an attenuated member of the tick-borne encephalitis virus (TBEV) subgroup, neurons do not rely on IRF7 for cell-intrinsic antiviral resistance and IFN-I induction. An increased viral replication in IRF7-deficient mice suggests an indirect antiviral mechanism. Astrocytes rely on IRF7 to establish a cell-autonomous antiviral response. Notably, the loss of IRF7 particularly in astrocytes resulted in a high IFN-I production. Sustained production of IFN-I in astrocytes is independent of an IRF7-mediated positive feedback loop. IFN-I induction in the CNS is profoundly regulated in a cell type-specific fashion.
Sections du résumé
BACKGROUND
BACKGROUND
Type I interferons (IFN-I) are fundamental in controlling viral infections but fatal interferonopathy is restricted in the immune-privileged central nervous system (CNS). In contrast to the well-established role of Interferon Regulatory Factor 7 (IRF7) in the regulation of IFN-I response in the periphery, little is known about the specific function in the CNS.
METHODS
METHODS
To investigate the role for IRF7 in antiviral response during neurotropic virus infection, mice deficient for IRF3 and IRF7 were infected systemically with Langat virus (LGTV). Viral burden and IFN-I response was analyzed in the periphery and the CNS by focus formation assay, RT-PCR, immunohistochemistry and in vivo imaging. Microglia and infiltration of CNS-infiltration of immune cells were characterized by flow cytometry.
RESULTS
RESULTS
Here, we demonstrate that during infection with the neurotropic Langat virus (LGTV), an attenuated member of the tick-borne encephalitis virus (TBEV) subgroup, neurons do not rely on IRF7 for cell-intrinsic antiviral resistance and IFN-I induction. An increased viral replication in IRF7-deficient mice suggests an indirect antiviral mechanism. Astrocytes rely on IRF7 to establish a cell-autonomous antiviral response. Notably, the loss of IRF7 particularly in astrocytes resulted in a high IFN-I production. Sustained production of IFN-I in astrocytes is independent of an IRF7-mediated positive feedback loop.
CONCLUSION
CONCLUSIONS
IFN-I induction in the CNS is profoundly regulated in a cell type-specific fashion.
Identifiants
pubmed: 37737190
doi: 10.1186/s12974-023-02892-w
pii: 10.1186/s12974-023-02892-w
pmc: PMC10515022
doi:
Substances chimiques
Antibodies
0
Interferon Regulatory Factor-7
0
Interferon Type I
0
Irf7 protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
213Subventions
Organisme : The Federal state of Saxony-Anhalt and the European Structural and Investment Fund
ID : ZS/2019/07/99748
Organisme : The federal state Saxony-Anhalt and the European Structural and Investment Fund
ID : ESF, 2014-202, ZS/2016/08/80645
Organisme : The federal state Saxony-Anhalt and the European Structural and Investment Fund
ID : ZS/2016/08/80645
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB854 A29N
Organisme : German ministry of Education and Research
ID : TBENAGER 01KI1728H
Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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