Mannose-binding lectin (MBL) is an important constituent-of the innate immu
ne system. This protein binds through multiple lectin domains to the repeat
ing sugar arrays that decorate many microbial:surfaces, and is then able to
activate the complement system through-a specific protease called MEL-asso
ciated protease-2. We have used flow cytometry to study both the binding of
MBL to microorganisms and the subsequent activation of complement. For sel
ected Gram-negative organisms, such as Salmonella and Neisseria, we have ex
amined the relative roles of lipopolysaccharide (LPS) structure and capsule
in determining binding and conclude that the LPS is of major importance. O
ur results from studies with several clinically relevant organisms also sho
w that MBL binding detected by flow cytometry leads to measurable activatio
n of purified C4, suggesting that the. bound lectin is capable-of initiatin
g opsonophagocytosis and/or bacterial lysis. There is an increasing literat
ure suggesting that MBL deficiency, which mainly results from three relativ
ely common single point mutations in exon I of the gene, predisposes both t
o infection by extracellular pathogens and to autoimmune disease. In additi
on, the protein also modulates disease severity, at least in part through a
complex, dose-dependent influence on cytokine production. The mechanisms a
nd signalling pathways involved in such processes remain to be elucidated.