Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
PLoS Pathog
; 8(8): e1002841, 2012.
Article
em En
| MEDLINE
| ID: mdl-22916010
ABSTRACT
Intracellular Toll-like receptors (TLRs) expressed by dendritic cells recognize nucleic acids derived from pathogens and play an important role in the immune responses against the influenza virus (IAV), a single-stranded RNA sensed by different receptors including TLR7. However, the importance of TLR7 processing in the development of anti-viral immune responses is not known. Here we report that asparagine endopeptidase (AEP) deficient mice are unable to generate a strong anti-IAV response, as demonstrated by reduced inflammation, cross presentation of cell-associated antigens and priming of CD8(+) T cells following TLR7-dependent pulmonary infection induced by IAV. Moreover, AEP deficient lung epithelial- or myeloid-cells exhibit impaired TLR7 signaling due to defective processing of this receptor. Indeed, TLR7 requires a proteolytic cleavage by AEP to generate a C-terminal fragment competent for signaling. Thus, AEP activity is critical for TLR7 processing, opening new possibilities for the treatment of influenza and TLR7-dependent inflammatory diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endopeptidases
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Glicoproteínas de Membrana
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Transdução de Sinais
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Infecções por Orthomyxoviridae
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Linfócitos T CD8-Positivos
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Receptor 7 Toll-Like
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Vírus da Influenza A Subtipo H1N1
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article