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Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Aug 30; Vol. 12, pp. 714821. Date of Electronic Publication: 2021 Aug 30 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- The Fas/FasL pathway plays a key role in immune homeostasis and immune surveillance. In the central nervous system (CNS) Fas/FasL is involved in axonal outgrowth and adult neurogenesis. However, little is known about the role of the Fas/FasL pathway in herpes encephalitis. In this study, we used a neuropathogenic clinical strain of herpes simplex virus type 1 (HSV-1) to explore infection-induced inflammation and immune responses in the mouse brain and the role of Fas/FasL in antiviral CNS immunity. HSV-1 CNS infection induced the infiltration of Fas- FasL-bearing monocytes and T cells in the brain and also to an up-regulation of Fas and FasL expression on resident astrocytes and microglia within infected sites. Upon infection, Fas- and FasL-deficient mice (lpr and gld) were partially protected from encephalitis with a decreased morbidity and mortality compared to WT mice. Fas/FasL deficiency promoted cell-mediated immunity within the CNS. Fas receptor stimulation abrogated HSV-1 induced activation and inflammatory reactions in microglia from WT mice, while lack of Fas or FasL led to a more pronounced activation of monocytes and microglia and also to an enhanced differentiation of these cells into a pro-inflammatory M1 phenotype. Furthermore, the specific immune system was more efficient in Fas- and FasL-deficient mice with significantly higher numbers of infiltrating HSV-1-specific cytotoxic T cells in the brain. Our data indicate that the Fas/FasL pathway leads to excessive neuroinflammation during HSV-1 infection, which is associated with a diminished anti-viral response and an excessive neuroinflammation.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Krzyzowska, Kowalczyk, Skulska, Thörn and Eriksson.)
- Subjects :
- Animals
Biomarkers
Chemokines metabolism
Cytokines metabolism
Disease Models, Animal
Disease Susceptibility immunology
Encephalitis, Herpes Simplex diagnosis
Fas Ligand Protein genetics
Humans
Mice
Mice, Knockout
Microglia immunology
Microglia metabolism
Neuroinflammatory Diseases diagnosis
fas Receptor genetics
Encephalitis, Herpes Simplex etiology
Encephalitis, Herpes Simplex metabolism
Fas Ligand Protein metabolism
Herpesvirus 1, Human physiology
Neuroinflammatory Diseases etiology
Neuroinflammatory Diseases metabolism
fas Receptor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34526992
- Full Text :
- https://doi.org/10.3389/fimmu.2021.714821