Cyclophilin D Regulates Antiviral CD8+ T Cell Survival in a Cell-Extrinsic Manner.
Immunohorizons
; 4(4): 217-230, 2020 04 24.
Article
em En
| MEDLINE
| ID: mdl-32332052
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sobrevivência Celular
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Linfócitos T CD8-Positivos
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Interações entre Hospedeiro e Microrganismos
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Peptidil-Prolil Isomerase F
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Coriomeningite Linfocítica
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Vírus da Coriomeningite Linfocítica
Limite:
Animals
Idioma:
En
Revista:
Immunohorizons
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Canadá