Thioesterase PPT1 balances viral resistance and efficient T cell crosspriming in dendritic cells.
J Exp Med
; 216(9): 2091-2112, 2019 09 02.
Article
em En
| MEDLINE
| ID: mdl-31262842
Conventional type 1 dendritic cells (cDC1s) are inherently resistant to many viruses but, paradoxically, possess fewer acidic phagosomes that enable antigen retention and cross-presentation. We report that palmitoyl-protein thioesterase 1 (PPT1), which catabolizes lipid-modified proteins in neurons, is highly expressed in cDC1s. PPT1-deficient DCs are more susceptible to vesicular stomatitis virus (VSV) infection, and mice with PPT1 deficiency in cDC1s show impaired response to VSV. Conversely, PPT1-deficient cDC1s enhance the priming of naive CD8+ T cells into tissue-resident KLRG1+ effectors and memory T cells, resulting in rapid clearance of tumors and Listeria monocytogenes Mechanistically, PPT1 protects steady state DCs from viruses by promoting antigen degradation and endosomal acidification via V-ATPase recruitment. After DC activation, immediate down-regulation of PPT1 is likely to facilitate efficient cross-presentation, production of costimulatory molecules and inflammatory cytokines. Thus, PPT1 acts as a molecular rheostat that allows cDC1s to crossprime efficiently without compromising viral resistance. These results suggest potential therapeutics to enhance cDC1-dependent crosspriming.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tioléster Hidrolases
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Células Dendríticas
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Linfócitos T
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Vesiculovirus
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Apresentação Cruzada
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Estomatite Vesicular
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Resistência à Doença
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article