Ficolins: innate immune recognition proteins for danger sensing

Ficolins are oligomeric defence proteins assembled from collagen-like stalks and fibrinogen-like domains that are able to sense danger signals such as pathogen- or apoptotic cell-associated molecular patterns. In humans, L- and H-ficolins have been characterized in serum whereas M-ficolin is secreted by monocytic cells. Like mannan-binding lectin (MBL), they are able to associate with MBL-associated serine proteases and to trigger activation of the lectin pathway of complement, a major effector system of humoral innate immunity. They can also act as opsonins to enhance clearance of their targets by phagocytosis. Recent structural studies have shown that L-ficolin is a versatile recognition protein able to bind acetylated molecules and neutral carbohydrates through different binding sites, whereas H-ficolin has a single binding site with a more restricted specificity for neutral carbohydrates. Phylogenetic studies reveal that ficolins have been conserved through evolution, supporting the hypothesis that the primitive complement system was a lectin-based opsonic system, and emphasizing the essential role of carbohydrate recognition proteins in innate immunity.