Mannose-binding lectin / MBL is a pattern recognition molecule of the innate immune system. It belongs to the collectin family of proteins in which lectin (carbohydrate-recognition) domains are found in association with collagenous structures. In human, these proteins include serum MBL, lung surfactant protein A (SP-A) and lung surfactant protein D (SP-D). Mannose Binding Lectin / MBL is a liver-derived serum protein and is secreted into the serum, where it can activate an immune response before the induction of antigen-specific immunity.
MBL binds to a range of sugars including N-acetyl-d-glucosamine, mannose, N-acetyl-mannosamine, fucose and glucose. This permits the protein to interact with a wide selection of viruses, bacteria, yeasts, fungi and protozoa decorated with such sugars. Unlike the other collectins, MBL bound to microbial surfaces is able to activate the complement system in an antibody and C1-independent manner. This activation is mediated by complexes of MBL with a serine protease called MBL-associated serine protease 2 (MASP-2), which specifically cleaves C4 and C2 to create a C3 convertase enzyme. MBL may also interact directly with cell surface receptors and thereby promote opsonophagocytosis by a complement-independent pathway.
Mannose-binding lectin / MBL deficiency is one of the most common human immunodeficiencies and arises primarily from three single point mutations in exon 1 of the MBL-2 gene. These mutations result in a failure to assemble fully functional multimeric protein.
Several studies have shown that deficiency of Mannose-binding lectin / MBL increases the overall susceptibility of an individual to infectious disease. The most striking example of this is the association of acute respiratory tract infections with MBL deficiency in early childhood. In contrast, there is evidence that for some intracellular parasites Mannose-binding lectin / MBL deficiency may be protective and this might explain the high frequency of Mannose-binding lectin / MBL mutations in sub-Saharan Africa and South America.
Increasingly, there is evidence that the association between MBL levels and disease is complex. For example, the protein appears to influence the severity of several diseases. The mechanism whereby MBL exerts such effects is unclear but one possibility is through a dose-dependent modulation of pro-inflammatory cytokines.
1. Turner, M. W. (2003). The role of mannose-binding lectin in health and disease. Molecular immunology, 40(7), 423-429.
2. Takahashi K, et al. (2005). The role of the mannose-binding lectin in innate immunity. Clinical Infectious Diseases, 41(Supplement 7), S440-S444.