Abstract
The efficient spread of SARS-CoV-2 resulted in a unique pandemic in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. These data have been then confirmed using authentic SARS-CoV-2 virus and human respiratory cell lines. Thus, we described a mechanism potentiating viral spreading of infection.
Highlights
C-type Lectin Receptors (CLRs) are Pathogen Recognition Receptors (PRRs) involved in the detection of carbohydrate-based pathogen-associated molecular patterns by antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), and in the elaboration of the immune response [1,2]
We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in respiratory mucosa and lung tissue
Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ Vero E6 cells
Summary
C-type Lectin Receptors (CLRs) are Pathogen Recognition Receptors (PRRs) involved in the detection of carbohydrate-based pathogen-associated molecular patterns by antigen-presenting cells (APCs), including macrophages and dendritic cells (DCs), and in the elaboration of the immune response [1,2]. CLRs such as Dectin-2, Mincle, MGL (Macrophage galactose lectin), Langerin and DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) are major players in the recognition of pathogenic fungi, bacteria, parasites and viruses [3,4,5,6]. The interaction of these CLRs with their ligands allows DCs to modulate the immune response towards either activation or tolerance [7].
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