| text |
Mannose-binding lectin (MBL2), a soluble pattern recognition receptor that recognizes and binds specific surface-bound carbohydrate motifs, such as mannose and fucose, in a CaČ?-dependent manner (Turner MW, 1996; Neth O et al., 2000), binds to the spike (S) protein of SARS-CoV-2 (Ali YM et al., 2021; Stravalaci M et al., 2022; Hurler L et al., 2023; Bayarri-Olmos R et al., 2024). The heavily glycosylated viral S contains several oligomannose-type N-glycans (?Watanabe Y et al., 2020; Wang D et al., 2023), which serve as potential binding sites of MBL2 (Stravalaci M et al., 2022; Bayarri-Olmos R et al., 2024). The viral S protein is incorporated into mature virions as a structural component within the S3:M:E:encapsidated SARS coronavirus genomic RNA:7a:O-glycosyl 3a tetramer complex (Yao H et al., 2020; Yan W et al., 2022). MBL2 binding can sterically hinder the interaction between the viral S protein and its receptor, angiotensin-converting enzyme 2 (ACE2), thereby limiting viral entry into host cells (Stravalaci M et al., 2022). Upon binding to the viral S protein, MBL2 activates the lectin pathway of the complement cascade by associating with MBL-associated serine proteases (MASP1 and MASP2), leading to opsonization, membrane attack complex (MAC) formation, and enhanced viral clearance (Ali YM et al., 2021; Stravalaci M et al., 2022). In addition, the nucleocapsid (N) protein of SARS-CoV-2 is thought to contribute to MBL-dependent, MASP2-mediated activation of the lectin pathway (Ali YM et al., 2021; Gao T et al., 2022). However, the precise mechanism of N protein involvement remains unclear, with studies reporting contradictory findings (Bally I et al., 2024; Kocsis A et al., 2024). Complement activation via MBL2 also contributes to the production of pro-inflammatory anaphylatoxins (C3a and C5a), which recruit immune cells and amplify cytokine production. Although complement activation supports viral clearance, excessive or uncontrolled activation may promote hyperinflammation and tissue injury, implicating the lectin pathway in COVID-19-related-immunopathologies (Rambaldi A et al., 2020; Medetalibeyoglu A et al., 2021; Stravalaci M et al., 2022; Hurler L et al., 2023; Bulla R et al., 2023; Takenaka H et al., 2023).
|
