Siglec-11

Siglec-11 is a human-specific inhibitory Siglec of the CD33-related family, notable for being one of the few genes that emerged after divergence from the chimpanzee lineage, having arisen from gene conversion between SIGLECL1 and SIGLECP genes on chromosome 19. Siglec-11 is a type I transmembrane protein whose V-set domain binds α2,8-linked disialic acid structures, including disialylated gangliosides such as GD3 and GT1b, an unusual specificity shared with Siglec-7 but achieved through a different binding-site architecture. Siglec-11 expression in adults is essentially restricted to tissue macrophages, including brain microglia, where its ITIM-bearing cytoplasmic tail recruits SHP-1 to suppress inflammatory activation. Siglec-11 rose to prominence in human evolution studies because it is expressed in microglia and appears to modulate neuroinflammation: sialylated ligands in the brain engaging Siglec-11 dampen microglial toxicity toward neurons, and the gene's emergence correlates with lineage-specific brain evolution. Siglec-11 also interacts with sialylated pathogens: group B Streptococcus sialylated capsule engages Siglec-11 to suppress macrophage immune responses, illustrating pathogen mimicry of this receptor-ligand system.