Critical role for asparagine endopeptidase in endocytic Toll-like receptor signaling in dendritic cells.
Immunity
; 31(5): 737-48, 2009 Nov 20.
Article
en En
| MEDLINE
| ID: mdl-19879164
ABSTRACT
Intracellular Toll-like receptor 3 (TLR3), TLR7, and TLR9 localize in endosomes and recognize single-stranded RNA and nucleotides from viruses and bacteria. This interaction induces their conformational changes resulting in the production of proinflammatory cytokines and upregulation of cell surface molecules. TLR9 requires a proteolytic cleavage for its signaling. Here, we report that myeloid and plasmacytoid dendritic cells (DCs) deficient for the asparagine endopeptidase (AEP), a cysteine lysosomal protease, showed a decrease in the secretion of proinflammatory cytokines in response to TLR9 stimulation in vitro and in vivo. Upon stimulation, full-length TLR9 was cleaved into a 72 kDa fragment and this processing was strongly reduced in DCs lacking AEP. Processed TLR9 coeluted with the adaptor molecule MyD88 and AEP after size exclusion chromatography. When expressed in AEP-deficient DCs, the 72 kDa proteolytic fragment restored TLR9 signaling. Thus, our results identify an endocytic protease playing a critical role in TLR processing and signaling in DCs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Cisteína Endopeptidasas
/
Transducción de Señal
/
Receptor Toll-Like 9
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Francia