Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1ß via a noncanonical caspase-8 inflammasome.
Nat Immunol
; 13(3): 246-54, 2012 Jan 22.
Article
em En
| MEDLINE
| ID: mdl-22267217
ABSTRACT
Production of the proinflammatory cytokine interleukin 1ß (IL-1ß) by dendritic cells is crucial in host defense. Here we identify a previously unknown role for dectin-1 in the activation of a noncanonical caspase-8 inflammasome in response to fungi and mycobacteria. Dectin-1 induced both the production and maturation of IL-1ß through signaling routes mediated by the kinase Syk. Whereas the CARD9-Bcl-10-MALT1 scaffold directed IL1B transcription, the recruitment of MALT1-caspase-8 and ASC into this scaffold was crucial for processing of pro-IL-1ß by caspase-8. In contrast to activation of the canonical caspase-1 inflammasome, which requires additional activation of cytosolic receptors, activation of the noncanonical caspase-8 inflammasome was independent of pathogen internalization. Thus, dectin-1 acted as an extracellular sensor for pathogens that induced both IL-1ß production and maturation through a noncanonical caspase-8-dependent inflammasome for protective immunity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lectinas Tipo C
/
Caspase 8
/
Interleucina-1beta
/
Inflamassomos
Limite:
Humans
Idioma:
En
Revista:
Nat Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Holanda