Role of L-ficolin/mannose-binding lectin-associated serine protease complexes in the opsonophagocytosis of type III group B streptococci.
Serotype III group B streptococci (GBS) are a common cause of neonatal sepsis and meningitis. Although deficiency in maternal capsular polysaccharide (CPS)-specific IgG correlates with susceptibility of neonates to the GBS infection, serum deficient in CPS-specific IgG mediates significant opsonophagocytosis. This IgG-independent opsonophagocytosis requires activation of the complement pathway, a process requiring the presence of both Ca(2+) and Mg(2+), and is significantly reduced by chelating Ca(2+) with EGTA. In these studies, we defined a role of L-ficolin/mannose-binding lectin-associated serine protease (MASP) complexes in Ca(2+)-dependent, Ab-independent opsonophagocytosis of serotype III GBS. Incubation of GBS with affinity-purified L-ficolin/MASP complexes and C1q-depleted serum deficient in CPS-specific Ab supported opsonophagocytic killing, and this killing was inhibited by fluid-phase N-acetylglucosamine, the ligand for L-ficolin. Binding of L-ficolin was proportional to the CPS content of individual strains, and opsonophagocytic killing and C4 activation were inhibited by fluid-phase CPS, suggesting that L-ficolin binds to CPS. Sialic acid is known to inhibit alternative complement pathway activation, and, as expected, the bactericidal index (percentage of bacteria killed) for individual strains was inversely proportional to the sialic acid content of the CPS, and L-ficolin-initiated opsonophagocytic killing was significantly increased by addition of CPS-specific IgG2, which increased activation of the alternative pathway. We conclude that binding of L-ficolin/MASP complexes to the CPS generates C3 convertase C4b2a, which deposits C3b on GBS. C3b deposited by this lectin pathway forms alternative pathway C3 convertase C3bBb whose activity is enhanced by CPS-specific IgG2, leading to increased opsonophagocytic killing by further deposition of C3b on the GBS.
Aoyagi
Youko
Y
Division of Microbiology, Joshi-Eiyoh (Kagawa Nutrition) University, Sakado, Saitama 350-0288, Japan.
Adderson
Elisabeth E
EE
Min
Jin G
JG
Matsushita
Misao
M
Fujita
Teizo
T
Takahashi
Shinji
S
Okuwaki
Yoshiyuki
Y
Bohnsack
John F
JF
D000818:Animals; D003167:Complement Activation; D037582:Complement Pathway, Mannose-Binding Lectin / Q000502:physiology; D006801:Humans; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D050606:Mannose-Binding Protein-Associated Serine Proteases; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D013292:Streptococcus agalactiae / Q000276:immunology*; D000097604:Ficolins
D037102:Lectins; D050606:Mannose-Binding Protein-Associated Serine Proteases; D009895:Opsonin Proteins; D011135:Polysaccharides, Bacterial; D012697:Serine Endopeptidases; D000097604:Ficolins