A group from New York University Grossman School of Medicine, etc. has reported that C-type lectins expressed on myeloid cells induce proinflammatory responses through the interaction with SARS-CoV-2.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106883/
It was investigated that the binding of human immunoglobulin Fc-tagged SARS-CoV-2 S, S1, and RBD recombinant proteins to HEK293T cells transfected with individual cDNA including five C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2). It was clearly shown that the ectopic expression of the myeloid cell receptors in HEK293T cells supported SARS-CoV-2 engagement independently from ACE2. The binding of DC-SIGN, L-SIGN, ASGR1, and CLEC10A was not affected by soluble ACE2-His, but that of ACE2 and LSECtin was completely blocked by soluble ACE2-His, and also the binding of DC-SIGN and L-SIGN was completely inhibited by mannan.
Furthermore, GFP-encoding HIV-based lentivirus pseudotyped with SARS-CoV-2 S protein (SARS-CoV-2 pseudovirus) was used to evaluate binding to those myeloid cell receptors. In the presence of the SARS-CoV-2 pseudovirus, robust GFP signals were observed in HEK293T expressing ectopic DC-SIGN or L-SIGN as well as expressing ectopic ACE2. The low level of SARS-CoV-2 pseudovirus engagement through LSECtin, ASGR1, CLEC10A, and TTYH2 was enhanced by co-expression of furin and/or TMPRSS2, which mediate S protein cleavage for viral entry. Consistent with our S protein mannan blockade results, pseudovirus-derived GFP signals through DC-SIGN and L-SIGN were inhibited by mannan treatment. These data suggested that these myeloid cell receptors can engage with the SARS-CoV-2 S protein on the pseudotyped virus.
