C-Type Lectin-Like Receptors of the Dectin-1 Cluster: Ligands and Signaling Pathways

Abstract

Innate immunity is constructed around genetically encoded receptors that survey the intracellular and extracellular environments for signs of invading microorganisms. These receptors recognise the invader and through complex intracellular networks of molecular signaling, they destroy the threat whilst instructing effective adaptive immune responses. Many of these receptors, like the Toll-like receptors in particular, are well-known for their ability to mediate downstream responses upon recognition of exogenous or endogenous ligands; however, the emerging family known as the C-type lectin-like receptors contains many members that have a huge impact on immune and homeostatic regulation. Of particular interest here are the C-type lectin-like receptors that make up the Dectin-1 cluster and their intracellular signaling motifs that mediate their functions. In this review, we aim to draw together current knowledge of ligands, motifs and signaling pathways, present downstream of Dectin-1 cluster receptors, and discuss how these dictate their role within biological systems.

Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities

“…Phosphorylated ERK is an upstream mediator of ROS/RNS and is therefore indicative of immune-stimulation [29]. Figure 10 shows phosphorylated ERK generated after 5 min of [4].…”

Cell-surface C-type lectin-like receptor CLEC-1 dampens dendritic cell activation and downstream Th17 responses

“…Importantly, using CLEC-1-deficient rats, we showed that disruption of CLEC-1 signaling led to an enhanced Il12p40 subunit expression in DCs, and to an exacerbation of downstream in Introduction triggering, most CLRs expressed on DCs modulate nuclear factor-kB (NF-kB) activation via the spleen tyrosine kinase (SYK) signaling pathway to enhance or suppress cellular activation, and fine-tune the magnitude and quality of downstream T-cell responses. 3 We previously identified the CTLR, C-type lectin-like receptor-1 (CLEC-1), to be upregulated in a heart allograft model of tolerance in rats. 4 We demonstrated that CLEC-1 is expressed by rat myeloid and endothelial cells (ECs), and is downregulated by pro-inflammatory stimuli and enhanced by transforming growth factor b (TGF-b).…”

“…CLEC-1 does not contain an immunoreceptor tyrosine-based activation or inhibitory motif in the cytoplasmic tail, but rather a tyrosine residue in a noncharacterized signaling sequence [YSST], in addition to a tri-acidic motif [DDD]. 3,7 In humans, CLEC-1 protein was reported to be expressed intracellularly in ECs. 8 Nevertheless, its protein expression in human DCs as well as its biological effect remains uncharacterized.…”

“…3 We observed that CLEC-1 triggering on moDCs does not induce by itself nor does it modulate the expression of the activation markers CD80, CD86, CD83, and HLA-DR, or the production of tumor necrosis factor-a, IL-12p70, IL-6, IL-23, and IL-10 induced by TLR 4 ligand (TLR 4-L), zymosan (agonist of both DECTIN-1 and TLR 2) ( Figure 2B-C), TLR 3, and TLR 7 ligands (data not shown). Moreover, CLEC-1 triggering does not induce by itself nor does it modulate the zymosan-induced activation of the SYK-dependent canonical NF-kB pathway, evaluated by the phosphorylation of the NF-kB inhibitor IkBa (Ser32/36) and by its degradation ( Figure 2D).…”

“…Alternatively, CLEC-1 could antagonize the SYK-independent RAF-1 pathway. Interestingly, CLEC-1 contains in its cytoplasmic tail a triacidic motif [DDD], 3 which has been shown for other CLRs to promote RAF-1 signaling and to modulate PRRs pathways. [38][39][40] However, if this tri-acidic motif is functional for CLEC-1 is currently unknown.…”