Syk-coupled C-type lectins in immunity

Abstract

The Syk-coupled C-type lectin receptor Dectin-1 was the first non-Toll like receptor described that could mediate its own intracellular signalling. It was initially identified as important for the innate recognition of and response to fungal pathogens but later studies revealed that it is also involved in triggering adaptive immune responses. It subsequently emerged that Dectin-1 is one of a number of spleen tyrosine kinase-coupled C-type lectin receptors that have been implicated not just in fungal immunity, but also in viral, mycobacterial and helminth infections. Here, we consider the ability of these receptors to trigger different aspects of immunity and highlight their emerging roles in a number of infection scenarios.

Figure 1

Recognition of microbial ligands by immunorecpetor tyrosine activation motif (ITAM)-coupled C-type lectin receptors (CLRs) leads to intracellular signalling via Syk. The figure shows cartoon representations of Dectin-1, Dectin-2, Mincle and CLEC5a. Dectin-1 recognises fungi and mycobacteria. It contains a cytoplasmic ITAM-like motif and following ligand binding it is thought that Syk is recruited by bridging two monophosphorylated Dectin-1 molecules. Dectin-2 is implicated in the detection of fungi, mycobacteria and helminths. Mincle is implicated in the detection of fungi and mycobacteria. Ligation of both Dectin-2 and Mincle results in phosphorylation of the associated FcRγ chains, recruitment of Syk and activation of downstream signalling. CLEC5a recognises Dengue virions, resulting in the phosphorylation of the associated DAP12 adaptor and downstream signalling, presumably via recruitment of Syk. Broken arrows indicate the occurrence of downstream signalling. It should be noted that for some of these receptors there are also instances of Syk-independent signalling that are not shown here.