| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Division of Microbiology, Joshi-Eiyoh (Kagawa Nutrition) University, Sakado, Saitama, Japan;
Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105;
Institute of Glycotechnology and Department of Applied Biochemistry, Tokai University, Hiratsuka, Japan;
Department of Biochemistry, Fukushima Medical University, Fukushima, Japan; and
¶ Department of Pediatrics, University of Utah Health Sciences Center, Salt Lake City, UT 84132
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 Ca2+ and Mg2+, and is significantly reduced by chelating Ca2+ with EGTA. In these studies, we defined a role of L-ficolin/mannose-binding lectin-associated serine protease (MASP) complexes in Ca2+-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.
This article has been cited by other articles:
|
|
 |
|
  Y. Aoyagi, E. E. Adderson, C. E. Rubens, J. F. Bohnsack, J. G. Min, M. Matsushita, T. Fujita, Y. Okuwaki, and S. Takahashi L-Ficolin/Mannose-Binding Lectin-Associated Serine Protease Complexes Bind to Group B Streptococci Primarily through N-Acetylneuraminic Acid of Capsular Polysaccharide and Activate the Complement Pathway Infect. Immun., January 1, 2008; 76(1): 179 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Garlatti, L. Martin, E. Gout, J.-B. Reiser, T. Fujita, G. J. Arlaud, N. M. Thielens, and C. Gaboriaud Structural Basis for Innate Immune Sensing by M-ficolin and Its Control by a pH-dependent Conformational Switch J. Biol. Chem., December 7, 2007; 282(49): 35814 - 35820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Lewis, H. Cao, S. K. Patel, S. Diaz, W. Ryan, A. F. Carlin, V. Thon, W. G. Lewis, A. Varki, X. Chen, et al. NeuA Sialic Acid O-Acetylesterase Activity Modulates O-Acetylation of Capsular Polysaccharide in Group B Streptococcus J. Biol. Chem., September 21, 2007; 282(38): 27562 - 27571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Carlin, A. L. Lewis, A. Varki, and V. Nizet Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes J. Bacteriol., February 15, 2007; 189(4): 1231 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.-Y. C. Lin, A. Whiting, E. Adderson, S. Takahashi, D. M. Dunn, R. Weiss, P. H. Azimi, J. B. Philips III, L. E. Weisman, J. Regan, et al. Phylogenetic Lineages of Invasive and Colonizing Strains of Serotype III Group B Streptococci from Neonates: a Multicenter Prospective Study J. Clin. Microbiol., April 1, 2006; 44(4): 1257 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, Y. Endo, D. Iwaki, M. Nakata, M. Matsushita, I. Wada, K. Inoue, M. Munakata, and T. Fujita Human M-Ficolin Is a Secretory Protein That Activates the Lectin Complement Pathway J. Immunol., September 1, 2005; 175(5): 3150 - 3156. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
