CD33-related siglecs in the immune system

Abstract

Cells of the innate immune system such as mononuclear phagocytes express a wide range of surface receptors that mediate recognition events involving both the host and the pathogen. Many of these are lectin-like receptors that interact with carbohydrate ligands. The CD33-related sialic acid binding Ig-like lectins (siglecs) are recently discovered receptors of the innate immune system that are specialised for sialic acid recognition at the cell surface and which contain tyrosine-based signalling motifs in their intracellular domains. There are significant differences in the repertoire of CD33-related siglecs amongst mammalian species, reflecting rapid and ongoing evolution of the genes encoding these proteins. Despite these differences, the overall expression patterns on leucocyte subsets within the innate immune system are very similar, indicating a conserved role for these receptors in regulating innate immune responses. Detailed studies with different glycans have revealed unique as well as overlapping carbohydrate binding specificities of each siglec. However, all CD33-related siglecs are normally masked via c/5-interactions with sialic acids at the cell surface and this is likely to modulate trans interactions with ligands expressed on other cells. Some pathogens such as Neisseria meningitidis can also express sialic acid, and recent studies indicate that pathogen-associated sialic acids can also function as ligands for siglecs and enhance the interactions of pathogens with cells of the innate immune system. It is currently unknown whether these these interactions benefit the host, the pathogen or neither.