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

作者：Gringhuis, Sonja I.^*; Kaptein, Tanja M.; Wevers, Brigitte A.; Theelen, Bart; van der Vlist, Michiel; Boekhout, Teun; Geijtenbeek, Teunis B. H.

来源：Nature Immunology, 2012, 13(3): 246-U63.

DOI：10.1038/ni.2222

• T-CELL-ACTIVATION
• NLRP3 INFLAMMASOME
• FUNGAL-INFECTIONS
• HOST-DEFENSE
• PARACASPASE MALT1
• CANDIDA-ALBICANS
• DENDRITIC CELLS
• INNATE IMMUNITY
• INTERLEUKIN-17
• STIMULATION

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

• 出版日期2012-3