Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome

Nat Immunol. 2012 Jan 22;13(3):246-54. doi: 10.1038/ni.2222.

Abstract

Production of the proinflammatory cytokine interleukin 1β (IL-1β) 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-1β 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-1β 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-1β production and maturation through a noncanonical caspase-8-dependent inflammasome for protective immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / immunology
  • Caspase 8 / immunology*
  • Enzyme Activation
  • Extracellular Space / immunology
  • Humans
  • Inflammasomes / immunology*
  • Interleukin-1beta / immunology*
  • Lectins, C-Type / immunology*
  • Lectins, C-Type / metabolism
  • Mycobacterium / immunology
  • Signal Transduction

Substances

  • CLEC7A protein, human
  • Inflammasomes
  • Interleukin-1beta
  • Lectins, C-Type
  • CASP8 protein, human
  • Caspase 8