Abstract
The innate immune system is the body's first line of defense against pathogens and involves antibody and complement system-mediated antigen removal. Immune-response-related complement molecules have been identified in lamprey, and the occurrence of innate immune response via the mannose-binding lectin-associated serine proteases of the lectin cascade has been reported. We have previously shown that lamprey (Lampetra japonica) serum can efficiently and specifically eliminate foreign pathogens. Therefore, we aimed to understand the immune mechanism of lamprey serum in this study. We identified and purified a novel spherical lectin (LSSL) from lamprey serum. LSSL had two structural calcium ions coordinated with conserved amino acids, as determined through cryogenic electron microscopy. LSSL showed high binding capacity with microbial and mammalian glycans and demonstrated agglutination activity against bacteria. Phylogenetic analysis revealed that LSSL was transferred from phage transposons to the lamprey genome via horizontal gene transfer. Furthermore, LSSL was associated with mannose-binding lectin-associated serine protease 1 and promoted the deposition of the C3 fragment on the surface of target cells upon binding. These results led us to conclude that LSSL initiates and regulates agglutination, resulting in exogenous pathogen and tumor cell eradication. Our observations will give a greater understanding of the origin and evolution of the complement system in higher vertebrates and lead to the identification of novel immune molecules and pathways for defense against pathogens and tumor cells.