Dectin-1: a role in antifungal defense and consequences of genetic polymorphisms in humans

Abstract

The clinical relevance of fungal infections has increased dramatically in recent decades as a consequence of the rise of immunocompromised populations, and efforts to understand the underlying mechanisms of protective immunity have attracted renewed interest. Here we review Dectin-1, a pattern recognition receptor involved in antifungal immunity, and discuss recent discoveries of polymorphisms in the gene encoding this receptor which result in human disease.

Fig. 1

A schematic representation of the structure of Dectin-1

Fig. 2

Signaling pathway induced by Dectin-1. Upon ligand binding, Dectin-1 becomes tyrosine-phosphorylated by Src kinases, thereby providing a docking site for Syk which initiates downstream signaling. The downstream signaling is effected by molecules such as CARD9, Bcl10, and MALT1, which lead to NF-κB activation and cytokine production. Dectin-1 can also activate NFAT and noncanonical NF-κB in a CARD9-Bcl10-MALT1-independent manner. Stimulation of Dectin-1 with β-glucans can also induce a second Syk-independent signaling pathway mediated by the serine-threonine kinase Raf-1