Evolution of the lectin–complement pathway and its role in innate immunity

Lectins, which are carbohydrate-binding proteins, are important in innate immunity because they are able to recognize a wide range of pathogens. Two classes of collagenous lectin — mannose-binding lectin (MBL) and ficolins — can activate the complement system, which was identified originally as an antibody-dependent effector system. The complement system, which consists of more than 30 plasma and cell-surface proteins, is activated by three pathways — the classical, lectin and alternative pathways — which lead to the generation of opsonins and pathogen destruction. The classical pathway is activated by binding of the first complement component — which consists of C1q and two serine proteases (C1r and C1s) — to immune complexes, whereas the lectin pathway is activated by the recognition of carbohydrates on pathogens through MBL and ficolins, which are associated with novel serine proteases. MBL-associated serine proteases (MASPs), which share domain structure and several functions with the classical-pathway proteases C1r and C1s, are the proteolytic enzymes that are responsible for activation of the lectin pathway. The ascidian complement system — which consists of MBL-like lectin, ficolins, two MASPs, C3 and C3 receptor — functions in an opsonic manner, and it constitutes a primordial complement system that corresponds to the mammalian lectin pathway. Structural and functional similarities between the lectin–protease complex in the lectin pathway and the first component of the classical complement pathway indicate that the primitive lectin pathway in innate immunity might have evolved into the classical pathway to serve as an effector system of acquired immunity.