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Cyclophilin D Regulates Antiviral CD8(+) T Cell Survival in a Cell-Extrinsic Manner

Condotta, Stephanie A; Downey, Jeffrey; Pardy, Ryan D; Valbon, Stefanie F; Tarrab, Esther; Lamarre, Alain ORCID logoORCID: https://orcid.org/0000-0002-7913-871X; Divangahi, Maziar et Richer, Martin J (2020). Cyclophilin D Regulates Antiviral CD8(+) T Cell Survival in a Cell-Extrinsic Manner Immunohorizons , vol. 4 , nº 4. pp. 217-230. DOI: 10.4049/immunohorizons.2000016.

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Résumé

CD8+ T cell–mediated immunity is critical for host defense against viruses and requires mitochondria-mediated type I IFN (IFN-I) signaling for optimal protection. Cyclophilin D (CypD) is a mitochondrial matrix protein that modulates the mitochondrial permeability transition pore, but its role in IFN-I signaling and CD8+ T cell responses to viral infection has not been previously explored. In this study, we demonstrate that CypD plays a critical extrinsic role in the survival of Ag-specific CD8+ T cell following acute viral infection with lymphocytic choriomeningitis virus in mice. CypD deficiency resulted in reduced IFN-I and increased CD8+ T cell death, resulting in a reduced antiviral CD8+ T cell response. In addition, CypD deficiency was associated with an increase in pathogen burden at an early time-point following infection. Furthermore, our data demonstrate that transfer of wild-type macrophages (expressing CypD) to CypD-deficient mice can partially restore CD8+ T cell responses. These results establish that CypD plays an extrinsic role in regulating optimal effector CD8+ T cell responses to viral infection. Furthermore, this suggests that, under certain circumstances, inhibition of CypD function may have a detrimental impact on the host’s ability to respond to viral infection

Type de document: Article
Informations complémentaires: Article en accès libre via Unpaywall
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 15 juill. 2021 14:42
Dernière modification: 15 févr. 2022 18:45
URI: https://espace.inrs.ca/id/eprint/11565

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