Siglecs as positive and negative regulators of the immune system

Siglecs (sialic acid-binding Ig-like lectins) are mainly expressed in the immune system. Sn (sialoadhesin) (siglec-1), CD22 (siglec-2) and siglec-15 are well conserved, whereas the CD33-related siglecs are undergoing rapid evolution, as reflected in large differences in repertoires among the different mammals studied so far. In the present paper, we review recent findings on the signalling properties of the CD33-related siglecs and discuss the emergence of both inhibitory and activating forms of this family. We also discuss how Sn may function as a positive regulator of adaptive immune responses and its emerging role as an induced macrophage pattern-recognition molecule for sialylated pathogens, especially enveloped viruses.