Mannose-binding lectin deficiencies in infectious and inflammatory disorders

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Mannose-binding lectin (MBL) is a plasma protein belonging to the family of collectins, which are carbohydrate binding proteins (lectins) composed of a carbohydrate recognition domain and a collagen-like stalk domain. The MBL subunits associate to form multimeric complexes (resembling a bouquet of tulips) capable of recognizing carbohydrate patterns displayed at high density on bacteria, viruses, fungi, and protozoa but not mammalian cells. Upon binding, MBL activates the complement system leading to opsonization or direct killing of micro-organisms. The key role played by MBL in innate immune defence has led to the notion that MBL functions as an ante-antibody, which controls microbial invasion in the lag phase between infection and the generation of specific antibodies and cellular immunity. Surprisingly, a relatively large proportion of individuals (20–40%) in all the human populations studied carry either homo- or heterozygous mutations in the MBL2 gene, which results in low plasma levels of MBL. This MBL deficiency is not normally associated with disease in healthy individuals. It may result, however, in increased susceptibility to infections in immunocompromised individuals and in premature and young children. This notion has been confirmed by recent published works, reviewed in the present report, which also indicate that MBL deficiency is not only a susceptibility marker but also a disease modifier of a large number of infectious and inflammatory processes, including autoimmune diseases.

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