The three human ficolins (H-, L- and M-ficolin) and mannan-binding lectin are pattern recognition molecules of the innate immune system mediating activation of the lectin pathway of the complement system. These four human proteins bind to some microorganisms and may be involved in the resolution of infections. We investigated the binding selectivity by examining the binding of M-ficolin to a panel of more than 100 different streptococcal strains (Streptococcus pneumoniae and Streptococcus mitis) each expressing distinct polysaccharide structures. M-ficolin binding was observed for three strains only, the pneumococcal serotypes 19B and 19C and a single mitis strain expressing a similar polysaccharide structure. The bound M-ficolin, in association with MASP-2, mediated complement factor C4 cleavage. Binding to the bacteria was inhibitable by N-acetyl glucosamine indicating that the interaction with the bacterial surface takes place via the fibrinogen-like domain. The common N-acetyl mannosamine residue present in the structures of the four capsular polysaccharides of group 19 is linked via a phosphodiester bond. This residue is apparently not a ligand for M-ficolin since the lectin binds to two of the group 19 polysaccharides only. M-ficolin bound strongly to serotype 19B and 19C polysaccharides. In contrast to the serotypes 19A and 19F these two serotypes contain an extra N-acetyl mannosamine residue linked via glycoside linkage only. Thus, this extra residue seems to be the M-ficolin ligand.In conclusion, we were able to demonstrate specific binding of M-ficolin to some capsular polysaccharides of the opportunistic pathogen S. pneumoniae and of the commensal bacterium S. mitis.
Infection and Immunity, 2013, Vol 81, Issue 2, p. 452-459