mannosebinding

Mannose-binding refers to the recognition of mannose residues, which are common on the surfaces of many microbes, by specific proteins and receptors. The best-studied example is mannose-binding lectin (MBL), a soluble protein of the innate immune system.

MBL is a member of the collectin family and has a collagen-like domain linked to a carbohydrate recognition domain. It forms oligomeric complexes, often as trimers that assemble into higher-order structures. The carbohydrate recognition domain requires calcium ions to bind to mannose and related sugars such as N-acetylglucosamine, enabling selective interaction with microbial surfaces.

In immune defense, MBL binds to mannose-rich patterns on bacteria, fungi, viruses, and some parasites. Once bound, MBL associates with MBL-associated serine proteases (MASPs). Activation of MASPs initiates the lectin pathway of the complement system, leading to the cleavage of complement components C4 and C2 and the formation of the C3 convertase. This promotes opsonization, inflammation, and phagocytosis, enhancing microbial clearance. MBL can also act as an opsonin independent of complement.

Genetic and physiological aspects include the MBL2 gene, located on chromosome 10, which encodes MBL. Promoter and structural polymorphisms cause substantial variation in circulating MBL levels. Deficiency or low activity is relatively common in the population and can be associated with increased susceptibility to certain infections, especially in infancy or when other immune defects are present, though many individuals with low MBL are asymptomatic due to redundancy in immune pathways.

Beyond MBL, other mannose-binding receptors, such as the mannose receptor on macrophages, contribute to pathogen recognition and clearance through different mechanisms.