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.
Highlights
Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) found in humans [1,2]and their immune function is key to initiate immunity against invading viruses [3,4,5]
The discovery of the role of the receptor Siglec-1/CD169, a sialic acid-binding Ig-like lectin-1 expressed by DCs, has greatly contributed to our understanding of how viruses subvert DC activity
In addition to Plasmacytoid DCs (pDCs), myeloid DCs secrete type I IFNs, this release is mostly and indirectly triggered by immune activating signals present during the course of human immunodeficiency virus (HIV)-1 infection, which can induce the expression of IFN-stimulated genes on DCs in an autocrine manner [57,58,59,60]
Summary
Dendritic cells (DCs) are the most potent antigen presenting cells (APCs) found in humans [1,2]. Viral capture via Siglec-1 macrophages is necessary to elicit an effective antiviral CD8+ T cell response via antigen cross-presentation by DCs [35] Overall, these murine studies explain how Siglec-1 can contain viral replication and induce antiviral immunity against highly pathogenic viruses, and favor viral spread within tissues when retroviruses have a limited tropism. These murine studies explain how Siglec-1 can contain viral replication and induce antiviral immunity against highly pathogenic viruses, and favor viral spread within tissues when retroviruses have a limited tropism How these findings correlate with the pathogenesis of different Siglec-1-interacting human viruses, such as HIV-1 or EBOV, remains largely unexplored. We discuss how Siglec-1 is induced on human DCs upon viral infection, to what degree that impacts different viral antigen presentation routes, and in which ways distant enveloped viruses have evolved to exploit Siglec-1 function as a dissemination strategy in distinct anatomical compartments
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