CLEC7A

CLEC7A is a human gene that encodes Dectin-1, a type of C-type lectin receptor expressed primarily on myeloid cells such as macrophages, dendritic cells, neutrophils, and some epithelial cells. Dectin-1 functions as a pattern recognition receptor that detects fungal cell wall components, most notably beta-1,3-glucans found in organisms like Candida species, Aspergillus fumigatus, and Pneumocystis jirovecii. It can also recognize certain β-glucan-rich polysaccharides such as curdlan.

The receptor features an extracellular carbohydrate recognition domain that binds glucans, a stalk region, a transmembrane segment, and a cytoplasmic tail containing a hemITAM motif. Upon ligand binding, Dectin-1 recruits the Syk tyrosine kinase, initiating a signaling cascade through CARD9-BCL10-MALT1 that activates NF-kB and MAPK pathways. This signaling promotes phagocytosis, reactive oxygen species production, and the release of pro-inflammatory cytokines and chemokines, including TNF-α, IL-6, IL-1β, and IL-23. Dectin-1 signaling also supports dendritic cell maturation and helps drive Th17 responses, contributing to antifungal immunity and mucosal defense. Dectin-1 can act in concert with other pattern recognition receptors, such as TLR2, to amplify inflammatory responses.

Genetic variation in CLEC7A has been linked to altered susceptibility to fungal infections; for example, a common a premature stop codon variant can reduce Dectin-1 expression and function, increasing mucocutaneous candidiasis risk. Research continues into the role of CLEC7A in allergic and inflammatory diseases and its potential as a therapeutic target for modulating antifungal immunity.