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The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease

Journal

INTERNATIONAL REVIEWS OF IMMUNOLOGY
Volume 42, Issue 2, Pages 113-138

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/08830185.2021.1931171

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Siglec-1, also known as Sialoadhesin (Sn) and CD169, is a large member of the Siglec family expressed mainly on dendritic cells, macrophages, and interferon induced monocytes. It has a unique structure and function, allowing it to internalize antigens and pass them on to lymphocytes. It plays a key role in multiple human disease states, particularly bacterial and viral infections.
Siglec-1, also known as Sialoadhesin (Sn) and CD169 is highly conserved among vertebrates and with 17 immunoglobulin-like domains is Siglec-1 the largest member of the Siglec family. Expression of Siglec-1 is found primarily on dendritic cells (DCs), macrophages and interferon induced monocyte. The structure of Siglec-1 is unique among siglecs and its function as a receptor is also different compared to other receptors in this class as it contains the most extracellular domains out of all the siglecs. However, the ability of Siglec-1 to internalize antigens and to pass them on to lymphocytes by allowing dendritic cells and macrophages to act as antigen presenting cells, is the main reason that has granted Siglec-1's key role in multiple human disease states including atherosclerosis, coronary artery disease, autoimmune diseases, cell-cell signaling, immunology, and more importantly bacterial and viral infections. Enveloped viruses for example have been shown to manipulate Siglec-1 to increase their virulence by binding to sialic acids present on the virus glycoproteins allowing them to spread or evade immune response. Siglec-1 mediates dissemination of HIV-1 in activated tissues enhancing viral spread via infection of DC/T-cell synapses. Overall, the ability of Siglec-1 to bind a variety of target cells within the immune system such as erythrocytes, B-cells, CD8+ granulocytes and NK cells, highlights that Siglec-1 is a unique player in these essential processes.

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