imprint:
Springer Science and Business Media LLC, 2023
Published in:Journal of Neuroinflammation
Language:
English
DOI:
10.1186/s12974-023-02892-w
ISSN:
1742-2094
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>IFN-I induction in the CNS is profoundly regulated in a cell type-specific fashion.</jats:p>
</jats:sec>