Figure 2.

Transmembrane CLRs involved in antifungal immunity and their intracellular signaling pathways. Dectin-1, Dectin-2 and Mincle induce intracellular signaling via tyrosine (Y)-based activation motifs (immunoreceptor tyrosine-based activation motifs or ITAMs) which recruit and activate Syk-kinase either directly, or indirectly through the FcγR adaptor chain. Signaling through protein-kinase C (PKC)δ, this pathway activates the Card9-Bcl10-Malt1 complex inducing gene transcription and the production of various inflammatory mediators. DC-SIGN and Dectin-1 can signal via the Raf-1 kinase pathway which modulates (dotted line) other signaling pathways, including those induced by the Toll-like receptors (TLR) and the Dectin-1/ Syk pathway. The mannose receptor (MR) can also induce intracellular signaling, but the mechanisms involved are unknown. CLR signaling can collaborate with that of the TLR (red bi-arrow), to synergistically induce or repress the induction of various cytokines and chemokines. CLR can also mediate fungal phagocytosis and induction of anti-microbial effector mechanisms (not shown).