Reactome | CLEC7A/inflammasome pathway

CLEC7A/inflammasome pathway

Stable Identifier

R-HSA-5660668

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane, cytosol

ReviewStatus

5/5

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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
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
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