Abstract

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.

摘要

Siglec-1，也称为 Sialoadhesin (Sn) 和 CD169，在脊椎动物中高度保守，Siglec-1 具有 17 个免疫球蛋白样结构域，是 Siglec 家族中最大的成员。Siglec-1 的表达主要存在于树突细胞 (DC)、巨噬细胞和干扰素诱导的单核细胞上。Siglec-1 的结构在 siglec 中是独一无二的，它作为受体的功能也不同于此类中的其他受体，因为它包含所有 siglec 中最多的细胞外结构域。然而，Siglec-1 将抗原内化并通过允许树突细胞和巨噬细胞充当抗原呈递细胞将其传递给淋巴细胞的能力，是赋予 Siglec-1 在多种人类疾病状态（包括动脉粥样硬化）中发挥关键作用的主要原因, 冠状动脉疾病, 自身免疫性疾病, 细胞间信号传导、免疫学，更重要的是细菌和病毒感染。例如，包膜病毒已被证明可以通过与病毒糖蛋白上存在的唾液酸结合来操纵 Siglec-1 以增加其毒力，从而使它们能够传播或逃避免疫反应。Siglec-1 介导 HIV-1 在活化组织中的传播，通过感染 DC/T 细胞突触增强病毒传播。总体而言，Siglec-1 结合免疫系统内各种靶细胞（如红细胞、B 细胞、CD8+ 粒细胞和 NK 细胞）的能力突出表明，Siglec-1 在这些基本过程中发挥着独特的作用。例如，包膜病毒已被证明可以通过与病毒糖蛋白上存在的唾液酸结合来操纵 Siglec-1 以增加其毒力，从而使它们能够传播或逃避免疫反应。Siglec-1 介导 HIV-1 在活化组织中的传播，通过感染 DC/T 细胞突触增强病毒传播。总体而言，Siglec-1 结合免疫系统内各种靶细胞（如红细胞、B 细胞、CD8+ 粒细胞和 NK 细胞）的能力突出表明，Siglec-1 在这些基本过程中发挥着独特的作用。例如，包膜病毒已被证明可以通过与病毒糖蛋白上存在的唾液酸结合来操纵 Siglec-1 以增加其毒力，从而使它们能够传播或逃避免疫反应。Siglec-1 介导 HIV-1 在活化组织中的传播，通过感染 DC/T 细胞突触增强病毒传播。总体而言，Siglec-1 结合免疫系统内各种靶细胞（如红细胞、B 细胞、CD8+ 粒细胞和 NK 细胞）的能力突出表明，Siglec-1 在这些基本过程中发挥着独特的作用。