Mannose-binding lectin accelerates complement activation and increases serum killing of Neisseria meningitidis serogroup C.
The capacity for different lipo-oligosaccharide (LOS) sialylation patterns of Neisseria meningitidis serogroup C to influence the binding and function of the innate humoral component, mannose-binding lectin (MBL), was investigated. By use of flow cytometry and immunogold electron microscopy, a clinical isolate with reduced endogenous LOS sialylation was found to bind more MBL than did strains with higher endogenous sialylation. MBL binding was reduced but not ablated if the same strain was allowed to exogenously sialylate its LOS structures after incubation with cytidine-5'-monophospho-neuraminic acid. MBL binding led to an increased rate of complement activation, with enhanced deposition of the complement components C4 and C5b-9, and this correlated with an increase in bactericidal activity. LOS sialylation appears to be an important determinant of MBL binding to N. meningitidis and can modulate complement-dependent killing of the bacterium. These findings could explain the observed susceptibility to meningococcal disease of individuals genetically deficient in MBL.
Jack
D L
DL
Institute of Child Health, University College London, London, United Kingdom. D.L.Jack@sheffield.ac.uk
Jarvis
G A
GA
Booth
C L
CL
Turner
M W
MW
Klein
N J
NJ
D000209:Acute-Phase Proteins; D001770:Blood Bactericidal Activity; D002352:Carrier Proteins / Q000737:chemistry / Q000276:immunology*; D037222:Collectins; D003167:Complement Activation; D003181:Complement C4 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins; D008589:Meningococcal Infections / Q000382:microbiology; D008854:Microscopy, Electron; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D037222:Collectins; D003181:Complement C4; D015938:Complement Membrane Attack Complex; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D037102:Lectins; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein