C-Type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors

Abstract

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

Extracellular vimentin is an attachment factor that facilitates SARS-CoV-2 entry into human endothelial cells

“…In addition to its participation in infection, VIM also plays a critical role in lung inflammation and fibrosis through interaction with NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) (51). Expression of ACE2 in endothelial cells (52) and lung alveolar cells is relatively low (SI Appendix, Figs. S1 and S2), but VIM as an attachment factor produced by mesenchymal cells (e.g., endothelial and fibroblasts) (53), could enhance the SARS-CoV-2 entry in respiratory cells via both cisand trans-infection (44).…”

The seasonal behaviour of COVID-19 and its galectin-like culprit of the viral spike

“…We end by noting that lectins are a diverse family of proteins with the capacity to selectively recognize carbohydrate moieties associated for example with receptor proteins. It appears that the SARS-CoV-2 S-protein, besides binding ACE2, also interacts with the CRD of C-type lectin receptors, which facilitate viral entry by dysregulating host immune responses and acting as entry receptors ( Rahimi, 2021 ). A number of studies have recently surfaced that point into the centrality of lectin-mediated recognition ( Gao et al, 2021 ; Soh et al, 2021 ; Thépaut et al, 2021 ).…”

Adenovirus receptors on antigen‐presenting cells of the skin

“…DC SIGN, also known as CD209, is a member of the C-type Lectin Receptor (CLR) family and binds mannose groups with high affinity (Gao et al, 2020;Rahimi, 2020). CLRs are involved in tumor recognition, mannose recognition and antigen presentation.…”