Abstract
The capsular polysaccharide of type III group B streptococci contributes substantially to the virulence of this organism. We explored the extent to which capsular polysaccharide influences neutrophil complement receptor interactions by using a poorly encapsulated strain (COH 31r/s), two well-encapsulated strains (M732 and M912), and strains produced from COH 31r/s by transposon mutagenesis that lacked capsule (COH 31-15) or had capsular polysaccharide lacking terminal sialic acid residues (COH 31-21). When tested with normal human serum, each strain had initially high bactericidal indices (85 to 96%). Monoclonal antibody blockade of neutrophil complement receptor 3 (CD11b/CD18) inhibited opsonophagocytosis to a significantly greater extent for the well-encapsulated strain than for the poorly encapsulated, asialo, or unencapsulated mutant strain. The addition of antibody with specificity for capsular polysaccharide reduced the inhibitory effect significantly for the encapsulated but not for the mutant strains. Blockade of neutrophil complement receptor 1 (CD35) effected only low-level inhibition. However, simultaneous blockade of complement receptors 1 and 3 augmented the inhibitory effect. When hypogammaglobulinemic serum was used as an antibody-free complement source, the initial bactericidal index was low (30% +/- 15%) for an encapsulated strain and was not affected for the mutant strains. Blockade of either neutrophil complement receptor 1 or 3 or the combination fully inhibited killing of the encapsulated strain. These results demonstrate that the type III group B streptococcal capsular polysaccharide regulates interactions with neutrophil complement receptors. We conclude that efficient phagocytic killing of encapsulated group streptococci in nonimmune serum requires ligation of complement receptors 1 and 3.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anderson D. C., Hughes B. J., Smith C. W. Abnormal mobility of neonatal polymorphonuclear leukocytes. Relationship to impaired redistribution of surface adhesion sites by chemotactic factor or colchicine. J Clin Invest. 1981 Oct;68(4):863–874. doi: 10.1172/JCI110341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Anderson D. C., Schmalsteig F. C., Finegold M. J., Hughes B. J., Rothlein R., Miller L. J., Kohl S., Tosi M. F., Jacobs R. L., Waldrop T. C. The severe and moderate phenotypes of heritable Mac-1, LFA-1 deficiency: their quantitative definition and relation to leukocyte dysfunction and clinical features. J Infect Dis. 1985 Oct;152(4):668–689. doi: 10.1093/infdis/152.4.668. [DOI] [PubMed] [Google Scholar]
- Baker C. J., Kasper D. L. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N Engl J Med. 1976 Apr 1;294(14):753–756. doi: 10.1056/NEJM197604012941404. [DOI] [PubMed] [Google Scholar]
- Baker C. J., Kasper D. L., Davis C. E. Immunochemical characterization of the "native" type III polysaccharide of group B Streptococcus. J Exp Med. 1976 Feb 1;143(2):258–270. doi: 10.1084/jem.143.2.258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baker C. J., Kasper D. L., Edwards M. S., Schiffman G. Influence of preimmunization antibody levels on the specificity of the immune response to related polysaccharide antigens. N Engl J Med. 1980 Jul 24;303(4):173–178. doi: 10.1056/NEJM198007243030401. [DOI] [PubMed] [Google Scholar]
- Berger M., Sorensen R. U., Tosi M. F., Dearborn D. G., Döring G. Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis. J Clin Invest. 1989 Oct;84(4):1302–1313. doi: 10.1172/JCI114298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjornson A. B. Role of humoral factors in host resistance to the Bacteroides fragilis group. Rev Infect Dis. 1990 Jan-Feb;12 (Suppl 2):S161–S168. [PubMed] [Google Scholar]
- Brown E. J., Joiner K. A., Cole R. M., Berger M. Localization of complement component 3 on Streptococcus pneumoniae: anti-capsular antibody causes complement deposition on the pneumococcal capsule. Infect Immun. 1983 Jan;39(1):403–409. doi: 10.1128/iai.39.1.403-409.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell J. R., Baker C. J., Edwards M. S. Deposition and degradation of C3 on type III group B streptococci. Infect Immun. 1991 Jun;59(6):1978–1983. doi: 10.1128/iai.59.6.1978-1983.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dana N., Styrt B., Griffin J. D., Todd R. F., 3rd, Klempner M. S., Arnaout M. A. Two functional domains in the phagocyte membrane glycoprotein Mo1 identified with monoclonal antibodies. J Immunol. 1986 Nov 15;137(10):3259–3263. [PubMed] [Google Scholar]
- Edwards M. S., Baker C. J., Kasper D. L. Opsonic specificity of human antibody to the type III polysaccharide of group B Streptococcus. J Infect Dis. 1979 Dec;140(6):1004–1008. doi: 10.1093/infdis/140.6.1004. [DOI] [PubMed] [Google Scholar]
- Edwards M. S., Kasper D. L., Jennings H. J., Baker C. J., Nicholson-Weller A. Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci. J Immunol. 1982 Mar;128(3):1278–1283. [PubMed] [Google Scholar]
- Edwards M. S., Nicholson-Weller A., Baker C. J., Kasper D. L. The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus. J Exp Med. 1980 May 1;151(5):1275–1287. doi: 10.1084/jem.151.5.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fleming D. O. Mouse protection assay for group B streptococcus type III. Infect Immun. 1982 Jan;35(1):240–247. doi: 10.1128/iai.35.1.240-247.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fries L. F., Gaither T. A., Hammer C. H., Frank M. M. C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I. J Exp Med. 1984 Dec 1;160(6):1640–1655. doi: 10.1084/jem.160.6.1640. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gresham H. D., Graham I. L., Anderson D. C., Brown E. J. Leukocyte adhesion-deficient neutrophils fail to amplify phagocytic function in response to stimulation. Evidence for CD11b/CD18-dependent and -independent mechanisms of phagocytosis. J Clin Invest. 1991 Aug;88(2):588–597. doi: 10.1172/JCI115343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hostetter M. K. Serotypic variations among virulent pneumococci in deposition and degradation of covalently bound C3b: implications for phagocytosis and antibody production. J Infect Dis. 1986 Apr;153(4):682–693. doi: 10.1093/infdis/153.4.682. [DOI] [PubMed] [Google Scholar]
- Jennings H. J., Lugowski C., Kasper D. L. Conformational aspects critical to the immunospecificity of the type III group B streptococcal polysaccharide. Biochemistry. 1981 Aug 4;20(16):4511–4518. doi: 10.1021/bi00519a001. [DOI] [PubMed] [Google Scholar]
- Jennings H. J., Rosell K. G., Kasper D. L. Structural determination and serology of the native polysaccharide antigen of type-III group B Streptococcus. Can J Biochem. 1980 Feb;58(2):112–120. doi: 10.1139/o80-016. [DOI] [PubMed] [Google Scholar]
- Kasper D. L. Bacterial capsule--old dogmas and new tricks. J Infect Dis. 1986 Mar;153(3):407–415. doi: 10.1093/infdis/153.3.407. [DOI] [PubMed] [Google Scholar]
- Marques M. B., Kasper D. L., Pangburn M. K., Wessels M. R. Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect Immun. 1992 Oct;60(10):3986–3993. doi: 10.1128/iai.60.10.3986-3993.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michon F., Katzenellenbogen E., Kasper D. L., Jennings H. J. Structure of the complex group-specific polysaccharide of group B Streptococcus. Biochemistry. 1987 Jan 27;26(2):476–486. doi: 10.1021/bi00376a020. [DOI] [PubMed] [Google Scholar]
- Noya F. J., Baker C. J., Edwards M. S. Neutrophil Fc receptor participation in phagocytosis of type III group B streptococci. Infect Immun. 1993 Apr;61(4):1415–1420. doi: 10.1128/iai.61.4.1415-1420.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross G. D., Cain J. A., Lachmann P. J. Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin as functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol. 1985 May;134(5):3307–3315. [PubMed] [Google Scholar]
- Rubens C. E., Wessels M. R., Heggen L. M., Kasper D. L. Transposon mutagenesis of type III group B Streptococcus: correlation of capsule expression with virulence. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7208–7212. doi: 10.1073/pnas.84.20.7208. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shigeoka A. O., Hall R. T., Hemming V. G., Allred C. D., Hill H. R. Role of antibody and complement in opsonization of group B streptococci. Infect Immun. 1978 Jul;21(1):34–40. doi: 10.1128/iai.21.1.34-40.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shigeoka A. O., Rote N. S., Santos J. I., Hill H. R. Assessment of the virulence factors of group B streptococci: correlation with sialic acid content. J Infect Dis. 1983 May;147(5):857–863. doi: 10.1093/infdis/147.5.857. [DOI] [PubMed] [Google Scholar]
- Wessels M. R., Pozsgay V., Kasper D. L., Jennings H. J. Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. J Biol Chem. 1987 Jun 15;262(17):8262–8267. [PubMed] [Google Scholar]
- Wessels M. R., Rubens C. E., Benedí V. J., Kasper D. L. Definition of a bacterial virulence factor: sialylation of the group B streptococcal capsule. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8983–8987. doi: 10.1073/pnas.86.22.8983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winkelstein J. A., Abramovitz A. S., Tomasz A. Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall. J Immunol. 1980 May;124(5):2502–2506. [PubMed] [Google Scholar]
- Yang K. D., Bathras J. M., Shigeoka A. O., James J., Pincus S. H., Hill H. R. Mechanisms of bacterial opsonization by immune globulin intravenous: correlation of complement consumption with opsonic activity and protective efficacy. J Infect Dis. 1989 Apr;159(4):701–707. doi: 10.1093/infdis/159.4.701. [DOI] [PubMed] [Google Scholar]
- Yeung M. K., Mattingly S. J. Biosynthetic capacity for type-specific antigen synthesis determines the virulence of serotype III strains of group B streptococci. Infect Immun. 1984 May;44(2):217–221. doi: 10.1128/iai.44.2.217-221.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
