Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease

Abstract

CD169, also known as Siglec1 or Sialoadhesin (Sn), is a surface adhesion molecule on human myeloid cells. Being part of the Siglec family, it acts as a receptor for sialylated molecular structures, which are found among various pathogenic and non-pathogenic ligands. Recent data suggest that CD169 may represent a promising new biomarker in acute respiratory and non-respiratory viral infections, such as SARS-CoV-2, Respiratory syncytial virus (RSV) and Human immunodeficiency virus (HIV). Therein lies a great potential to sufficiently differentiate viral from bacterial infection, which has been an incessant challenge in the clinical management of infectious disease. CD169 equips myeloid cells with functions, reaching far beyond pathogen elimination. In fact, CD169 seems to crosslink innate and adaptive immunity by antigen presentation and consecutive pathogen elimination, embodying a substantial pillar of immunoregulation. Yet, our knowledge about the kinetics, mechanisms of induction, signaling pathways and its precise role in host-pathogen interaction remains largely obscure. In this review, we describe the role of CD169 as a potentially novel diagnostic biomarker for respiratory viral infection by evaluating its strengths and weaknesses and considering host factors that are involved in pathogenesis of virus infection. Finally, this brief review aims to point out shortcomings of available evidence, thus, guiding future work revolving the topic.

The Blessed Union of Glycobiology and Immunology: A Marriage That Worked

“…In this work, we suggest that the binding of sialoglycoproteins with siglecs would be involved in this process [134] (Figure 4). A variety of other siglec interactions with viral, protozoan pathogens and bacteria have been described elsewhere [135][136][137][138][139]. In 2014, Jandus and colleagues demonstrated that siglec 7 exerts an essential function in tumor escape by disrupting the functions of natural killer cells [129].…”

“…In this work, we suggest that the binding of sialoglycoproteins with siglecs would be involved in this process [134] (Figure 4). A variety of other siglec interactions with viral, protozoan pathogens and bacteria have been described elsewhere [135][136][137][138][139]. Thanks to advances in the field of glycoimmunology, today we know many siglec genes and binding specificities are quickly evolving among primates, with crucial extant polymorphisms in human populations that may impact vulnerability to infectionassociated disorders [135].…”

“…In this work, we suggest that the binding of sialoglycoproteins with siglecs would be involved in this process [ 134 ] ( Figure 4 ). A variety of other siglec interactions with viral, protozoan pathogens and bacteria have been described elsewhere [ 135 , 136 , 137 , 138 , 139 ].…”

Sialoadhesin (CD169/Siglec-1) is an extended molecule that escapes inhibitory cis-interactions and synergizes with other macrophage receptors to promote phagocytosis

“…Furthermore, the carbohydrate binding properties and expression patterns of Sn are well conserved between rodents and humans, where it is expressed by macrophage subsets both under resting and inflammatory conditions [5,6]. Unlike most siglecs, Sn can function as a cellular interaction molecule and mediate trans interactions with ligands on other cells and sialylated pathogens when expressed naturally at the cell surface [7][8][9][10]. In contrast, other siglecs of the immune system are usually masked by cis-interactions with sialic acids co-expressed on the same cell [4,11].…”

Sialoadhesin (CD169/Siglec-1) is an extended molecule that escapes inhibitory cis-interactions and synergizes with other macrophage receptors to promote phagocytosis

“…Furthermore, the carbohydrate binding properties and expression patterns of Sn are well conserved between rodents and humans, where it is expressed by macrophage subsets both under resting and in ammatory conditions [5,6]. Unlike most siglecs, Sn can function as a cellular interaction molecule and mediate trans interactions with ligands on other cells and sialylated pathogens when expressed naturally at the cell surface [7][8][9][10]. In contrast, other siglecs of the immune system are usually masked by cis-interactions with sialic acids co-expressed on the same cell [4,11].…”