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

• Published in: Nature immunology Vol. 13; no. 3; pp. 246 - 254
• Main Authors: Gringhuis, Sonja I, Kaptein, Tanja M, Wevers, Brigitte A, Theelen, Bart, van der Vlist, Michiel, Boekhout, Teun, Geijtenbeek, Teunis B H
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2012; Nature Publishing Group
• Subjects: 631/250/255/1672; 631/250/256/2177; 631/250/262; 631/250/516; Antifungal agents; Biomedical and Life Sciences; Biomedicine; Candida albicans - immunology; Caspase 8 - immunology; Cytokines; Dendritic cells; Drug therapy; Enzyme Activation; Extracellular Space - immunology; Genetic aspects; Health aspects; Humans; Immunology; Infectious Diseases; Inflammasomes - immunology; Interleukin-1beta - immunology; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Mycobacterium - immunology; Mycoses; Physiological aspects; Risk factors; Signal Transduction; Netherlands
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.2222

Production of the proinflammatory cytokine IL-1β is crucial in host defense. Geijtenbeek and colleagues show that dectin-1 signaling in response to fungi and mycobacteria induces IL-1β maturation via a noncanonical caspase-8-dependent inflammasome. 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.