Novel insights in the physiological function of sialoadhesin as a downregulator of macrophage phagocytosis and its implications for viral infection

In 1985, sialoadhesin (Siglec-1, CD169) was first described as a non-phagocytic sheep erythrocyte receptor (SER) expressed on resident bone marrow macrophages. A lot has been learned since then, and sialoadhesin is now established as a sialic-acid binding immunoglobulin-like lectin (Siglec) which is only expressed on subsets of differentiated macrophages and on inflammatory monocytes and macrophages. Besides being involved in cell-cell and cell-matrix interactions, sialoadhesin can also bind several pathogens. The receptor is involved in the entry of Neisseria meningitides, and serves as an endocytic receptor for porcine reproductive and respiratory syndrome virus (PRRSV). Despite continuing research efforts, the physiological role of sialoadhesin remains unclear up until today. Several studies indicate that the receptor may play a role in antigen presentation, and may be involved in the regulation of T cell responses in disease settings. Currently, a lot of effort is being made at developing therapies that can specifically target macrophages. The recognition of sialoadhesin as an endocytic receptor prompted interest in this molecule as a target for macrophagedirected therapies, which was further supported by its restricted expression pattern and the absence of a soluble form. However, the effect of ligation of sialoadhesin on macrophage functioning is poorly studied, even though it might provide valuable insights in the physiological function of sialoadhesin, as well as indicate possible side effects of sialoadhesin-targeted therapie