When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses

Abstract

Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments.

Selective tumor antigen vaccine delivery to human CD169 + antigen-presenting cells using ganglioside-liposomes

“…Both molecules are expressed by perifollicular macrophages in the human spleen and by IFN-I–treated moDCs ( 21 , 58 , 68 ). They function as a receptor for a variety of pathogens, but are also adhesion molecules for immune cells and can mediate transinfection of viruses ( 67 , 69 ). As such, human CD169 + DC-SIGN + perifollicular macrophages function similarly as mouse CD169 + metallophilic marginal-zone macrophages, that is, they both capture and transfer antigen to other immune cells, such as DCs and B cells, to initiate antigen-specific adaptive immune responses ( 22 ).…”

Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

“…The binding of α2-3- and/or α2-6-linked sialic acids as cellular receptors recruited in the host cell entry processes was described in several viral families isolated from humans, including Adenoviridae , Picornaviridae , Reoviridae , Paramyxoviridae and Polyomaviridae [ 40 , 41 , 42 , 43 , 44 ]. In the context of the virus-host interaction, some viruses genera employ the sialic acid- and Siglec-based mechanisms that avoid or deactivates host defence after pathogen invasion and underlie in the pathogenesis of acquired immune deficiency syndrome (AIDS) [ 45 , 46 , 47 , 48 ].…”

CXCR4 and CXCR7 Signaling Pathways: A Focus on the Cross-Talk Between Cancer Cells and Tumor Microenvironment

“…DCs are the most potent antigen presenting cells (APCs) in the immune system ( 87 ). Immature DCs (iDCs) express CXCR4 to reach inflamed peripheral tissues ( 88 ).…”