CLEC7A/inflammasome pathway

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R-HSA-5660668
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Pathway
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Homo sapiens
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Antifungal immunity through the induction of T-helper 17 cells (TH17) responses requires the production of mature, active interleukin-1beta (IL1B). CLEC7A (dectin-1) through the SYK route induces activation of NF-kB and transcription of the gene encoding pro-IL1B via the CARD9-BCL10-MALT1 complex as well as the formation and activation of a MALT1-caspase-8-ASC complex that mediated the processing of pro-IL1B. The inactive precursor pro-IL1B has to be processed into mature bioactive form of IL1B and is usually mediated by inflammatory cysteine protease caspase-1. Gringhuis et al. showed that CLEC7A mediated processing of IL1B occurs through two distinct mechanisms: CLEC7A triggering induced a primary noncanonical caspase-8 inflammasome for pro-IL1B processing that was independent of caspase-1 activity, whereas some fungi triggered a second additional mechanism that required activation of the NLRP3/caspase 1 inflammasome. Unlike the canonical caspase-1 inflammasome, CLEC7A mediated noncanonical caspase-8-dependent inflammasome is independent of pathogen internalization. CLEC7A/inflammasome pathway enables the host immune system to mount a protective TH17 response against fungi and bacterial infection (Gringhuis et al. 2012, Cheng et al. 2011).

Literature References
PubMed ID Title Journal Year
22267217 Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1? via a noncanonical caspase-8 inflammasome

Gringhuis, SI, Kaptein, TM, Wevers, BA, Theelen, B, van der Vlist, M, Boekhout, T, Geijtenbeek, TB

Nat. Immunol. 2012
21531876 The dectin-1/inflammasome pathway is responsible for the induction of protective T-helper 17 responses that discriminate between yeasts and hyphae of Candida albicans

Cheng, SC, van de Veerdonk, FL, Lenardon, M, Stoffels, M, Plantinga, T, Smeekens, S, Rizzetto, L, Mukaremera, L, Preechasuth, K, Cavalieri, D, Kanneganti, TD, van der Meer, JW, Kullberg, BJ, Joosten, LA, Gow, NA, Netea, MG

J. Leukoc. Biol. 2011
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