1887

Chapter 13 : Interactions of with the Proteins of the Complement Pathways

Author: Margaret K. Hostetter1
VIEW AFFILIATIONS HIDE AFFILIATIONS
Affiliations: 1: Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, LMP 4085, P.O. Box 208064, New Haven, CT 06520-8064
Content Type: Monograph
Publication Year: 2004

Category: Bacterial Pathogenesis; Clinical Microbiology

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Preview Magnify
Zoom in
Zoomout

Interactions of with the Proteins of the Complement Pathways, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816537/9781555812973_Chap13-1.gif /docserver/preview/fulltext/10.1128/9781555816537/9781555812973_Chap13-2.gif

Abstract:

Thirty-three years later, the heat-stable, specific components of the opsonic interaction (antibodies) were distinguished from nonspecific, heat-labile serum proteins, now named complement. In the presence of antibody alone, the rate of neutrophil phagocytosis of serotype 3 was accelerated more than sevenfold by the addition of active complement proteins in fresh human serum. Mannose binding lectin (MBL), a member of the collectin family, exhibits the collagen-like domain and the carbohydrate recognition domain of the collectin family. The most compelling evidence for the role of innate immunity in defense against pneumococcal infection focuses on C3. Recent genetic investigations have identified a number of pneumococcal proteins that affect the activation, deposition, or cleavage of C3 so as to interfere with C3-mediated opsonization and phagocytosis. Deleting the choline-binding region of the family 2 PspA generated a mutant that failed to bind human lactoferrin but retained most of its complement deposition. Virulence was moderately attenuated. The gene is present in 75% or more of pneumococcal strains, but the encoded proteins are highly polymorphic and are divided into 11 groups. Studies of type 3 pneumococci, highly resistant to phagocytosis, also pointed to absorption of factor H from plasma and led to the isolation of Hic. Pneumococcal proteins that interact with components of the classical or alternative complement pathways are predominantly surface expressed (except for Pla), related if not completely conserved (e.g., CbpA, PspA, PspC, and Hic), and potently immunogenic.

Citation: Hostetter M. 2004. Interactions of with the Proteins of the Complement Pathways, p 201-210. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch13

Key Concept Ranking

Bacterial Proteins
0.5823934
Cell Wall Proteins
0.45689362
Factor H
0.41234252
0.5823934
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Interactions of Streptococcus pneumoniae with the Proteins of the Complement Pathways
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816537.chap13-1,webId=/content/author/10.1128/9781555816537.chap13-1,properties={foaf_givenname=Margaret K., foaf_name=Margaret K. Hostetter, foaf_surname=Hostetter, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555816537.chap13-aff1]]}]]
Citation: Hostetter M. 2004. Interactions of with the Proteins of the Complement Pathways, p 201-210. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch13
/content/10.1128/9781555816537.chap13.fig13-1
FIGURE 1

Diagram of complement-mediated opsonization and phagocytosis. AB, antibody.

10.1128/9781555816537/fig13-1_thmb.gif
10.1128/9781555816537/fig13-1.gif
Image of FIGURE 1
FIGURE 1

Diagram of complement-mediated opsonization and phagocytosis. AB, antibody.

Citation: Hostetter M. 2004. Interactions of with the Proteins of the Complement Pathways, p 201-210. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch13
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816537.chap13
1. Abeyta, M.,, G. G. Hardy,, and J. Yother. 2003. Genetic alteration of capsule type but not PspA type affects accessibility of surface-bound complement and surface antigens of Streptococcus pneumoniae. Infect. Immun. 71: 218– 225.
2. Alcantara, R. B.,, L. C. Preheim,, and M. J. Gentry-Nielsen. 2001. Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia. Infect. Immun. 69: 3569– 3575.
3. Alexander, J. E.,, A. M. Berry,, J. C. Paton,, J. B. Rubins,, P. W. Andrew,, and T. J. Mitchell. 1998. Amino acid changes affecting the activity of pneumolysin alter the behavior of pneumococci in pneumonia. Microb. Pathog. 24: 167– 174.
4. Alper, C. A.,, N. Abramson,, R. B. J. Johnston,, J. H. Jandl,, and F. S. Rosen. 1970. Increased susceptibility to infection associated with abnormalities of complement-mediated functions and of the third component of complement (C3). N. Engl. J. Med. 282: 349– 354.
5. Alper, C. A.,, H. R. Colten,, F. S. Rosen,, A. R. Rabson,, G. M. MacNab,, and J. S. S. Gear. 1972. Homozygous deficiency of C3 in a patient with repeated infections. Lancet ii: 1179– 1181.
6. Angel, C. S.,, M. Ruzek,, and M. K. Hostetter. 1994. Degradation of C3 by Streptococcus pneumoniae. J. Infect. Dis. 170: 600– 608.
7. Auerbach, H. S.,, R. Burger,, A. Dodds,, and H. R. Colten. 1990. Molecular basis of complement C3 deficiency in guinea pigs. J. Clin. Investig. 86: 96– 106.
8. Ballow, M.,, J. E. Shira,, L. Harden,, S. Y. Yang,, and N. K. Day. 1970. Complete absence of the third component of complement in man. J. Clin. Investig. 56: 703– 710.
9. Brooks-Walter, A.,, D. E. Briles,, and S. K. Hollingshead. 1999. The pspC gene of Streptococcus pneumoniae encodes a polymorphic protein, PspC, which elicits cross-reactive antibodies to PspA and provides immunity to pneumococcal bacteremia. Infect. Immun. 67: 6533– 6542.
10. Brown, J. S.,, T. Hussell,, S. M. Gilliland,, D. W. Holden,, J. C. Paton,, M. R. Ehrenstein,, M. J. Walport,, and M. Botto. 2002. The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice. Proc. Natl. Acad. Sci. USA 99: 16969– 16974.
11. Cheng, Q.,, D. Finkel,, and M. K. Hostetter. 2000. Novel purification scheme and functions for a C3-binding protein from Streptococcus pneumoniae. Biochemistry 39: 5450– 5457.
12. Circolo, A.,, G. Garnier,, W. Fukuda,, X. Wang,, T. Hidvegi,, A. J. Szalai,, D. E. Briles,, J. E. Volanakis,, R. A. Wetsel,, and H. R. Colten. 1999. Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology 42: 135– 149.
13. Dave, S.,, A. Brooks-Walter,, M. K. Pangburn,, and L. S. McDaniel. 2001. PspC, a pneumococcal surface protein, binds human factor H. Infect. Immun. 69: 3435– 3437.
14. Duthy, T. G.,, R. J. Ormsby,, E. Giannakis,, A. D. Ogunniyi,, U. H. Stroeher,, J. C. Paton,, and D. L. Gordon. 2002. The human complement regulator factor H binds pneumococcal surface protein PspC via short consensus repeats 13 to 15. Infect. Immun. 70: 5604– 5611.
15. Friedland, I. R.,, M. M. Paris,, S. Hickey,, S. Shelton,, K. Olsen,, J. C. Paton,, and G. H. McCracken. 1995. The limited role of pneumolysin in the pathogenesis of pneumococcal meningitis. J. Infect. Dis. 172: 805– 809.
16. Fujita, T. 2002. Evolution of the lectin-complement pathway and its role in innate immunity. Nat. Rev. Immunol. 2: 346– 353.
17. Gordon, D. L.,, G. M. Johnson,, and M. K. Hostetter. 1986. Ligand-receptor interactions in the phagocytosis of virulent Streptococcus pneumoniae by polymorphonuclear leukocytes. J. Infect. Dis. 154: 619– 626.
18. Griffioen, A. W.,, E. A. Toebes,, B. J. Zegers,, and G. T. Rijkers. 1992. Role of CR2 in the human adult and neonatal in vitro antibody response to type 4 pneumococcal polysaccharide. Cell. Immunol. 143: 11– 22.
19. Hammerschmidt, S.,, S. R. Talay,, P. Brandtzaeg,, and G. S. Chhatwal. 1997. SpsA, a novel pneumococcal surface protein with specific binding to secretory immunoglobulin A and secretory component. Mol. Microbiol. 25: 1113– 1124.
20. Hostetter, M. K. 1999. Opsonic and nonopsonic interactions of C3 with Streptococcus pneumoniae. Microb. Drug Resist. 5: 85– 89.
21. Hostetter, M. K. 1986. Serotypic variations among virulent pneumococci in deposition and degradation of covalently bound C3b: implications for phagocytosis and antibody production. J. Infect. Dis. 153: 682– 693.
22. Hostetter, M. K.,, R. A. Krueger,, and D. J. Schmeling. 1984. The biochemistry of opsonization: central role of the reactive thiolester of the third component of complement. J. Infect. Dis. 150: 653– 661.
23. Hostetter, M. K.,, M. L. Thomas,, F. S. Rosen,, and B. F. Tack. 1982. Binding of C3b proceeds by a transesterification reaction at the thiolester site. Nature 298: 72– 75.
24. Hummell, D. S.,, R. W. Berninger,, and A. Tomasz. 1981. The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway. J. Immunol. 127: 1287– 1289.
25. Ianelli, F.,, M. R. Oggioni,, and G. Pozzi. 2002. Allelic variation in the highly polymorphic locus pspC of Streptococcus pneumoniae. Gene 284: 63– 71.
26. Janulczyk, R.,, F. Ianelli,, A. G. Sjoholm,, G. Pozzi,, and L. Bjorck. 2000. Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function. J. Biol. Chem. 275: 37257– 37263.
27. Jarva, H.,, R. Janulczyk,, J. Hellwage,, P. F. Zipfel,, L. Bjorck,, and S. Meri. 2002. Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8-11 of factor H. J. Immunol. 168: 1886– 1894.
28. Johnson, M. K. 1977. Cellular location of pneumolysin. FEMS Microbiol. Lett. 2: 243– 245.
29. Jounblat, R.,, A. Kadioglu,, T. J. Mitchell,, and P. W. Andrew. 2003. Pneumococcal behavior and host responses during bronchopneumonia are affected differently by the cytolytic and complement-activating activities of pneumolysin. Infect. Immun. 71: 1813-– 1819.
30. Kanclerski, K.,, and R. Mollby. 1987. Production and purification of Streptococcus pneumoniae hemolysin (pneumolysin). J. Clin. Microbiol. 25: 222– 225.
31. Kiehl, M. G.,, H. Ostermann,, M. L. Thomas,, T. Birkfellner,, and J. Kienast. 1997. Inflammatory mediators in BAL fluid as markers of evolving pneumonia in leukocytopenic patients. Chest 112: 1214– 1220.
32. Law, S. A. K.,, T. M. Minich,, and R. P. Levine. 1981. The binding reaction between the third human complement protein and small molecules. Biochemistry 20: 7457– 7460.
33. Leitao, M. F.,, M. M. Vilela,, R. Rutz,, A. S. Grumach,, A. Condino-Neto,, and M. Kirschfink. 1997. Complement factor I deficiency in a family with recurrent infections. Immunopharmacology 38: 207– 213.
34. Madsen, M.,, Y. Lebenthal,, Q. Cheng,, B. L. Smith,, and M. K. Hostetter. 2000. A pneumococcal protein that elicits interleukin-8 from pulmonary epithelial cells. J. Infect. Dis. 181: 1330– 1336.
35. Mitchell, T. J.,, P. W. Andrew,, F. K. Saunders,, A. N. Smith,, and G. J. Boulnois. 1991. Complement activation and antibody binding by pneumolysin via a region of the toxin homologous to a human acute-phase protein. Mol. Microbiol. 5: 1883– 1888.
36. Neeleman, C.,, S. P. M. Geelen,, P. C. Aerts,, M. R. Daha,, T. E. Mollnes,, J. J. Roord,, G. Posthuma,, H. van Dijk,, and A. Fleer. 1999. Resistance to both complement activation and phagocytosis in type 3 pneumococci is mediated by the binding of complement regulatory protein factor H. Infect. Immun. 67: 4517– 4524.
37. Pangburn, M. K. 1989. Analysis of recognition in the alternative pathway of complement: evidence of polysaccharide size. J. Immunol. 142: 2766– 2770.
38. Paton, J. C.,, A. M. Berry,, R. A. Lock,, D. Hansman,, and P. A. Manning. 1986. Cloning and expression in Escherichia coli of the Streptococcus pneumoniae gene encoding pneumolysin. Infect. Immun. 54: 50– 55.
39. Ren, B.,, A. J. Szalai,, O. Thomas,, S. K. Hollingshead,, and D. E. Briles. 2003. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect. Immun. 71: 75– 85.
40. Rosenow, C.,, P. Ryan,, J. N. Weiser,, S. Johnson,, P. Fontan,, A. Ortqvist,, and H. R. Masure. 1997. Contribution of novel cholinebinding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae. Mol. Microbiol. 25: 819– 829.
41. Rubins, J. B.,, D. Charboneau,, J. C. Paton,, T. J. Mitchell,, P. W. Andrew,, and E. F. Janoff. 1995. Dual function of pneumolysin in the early pathogenesis of murine pneumococcal pneumonia. J. Clin. Investig. 95: 142– 150.
42. Sahu, A.,, T. R. Kozel,, and M. K. Pangburn. 1994. Specificity of the thioester-containing reactive site of human C3 and its significance to complement activation. Biochem. J. 302: 429– 436.
43. Sahu, A.,, and M. K. Pangburn. 1995. Tyrosine is a potential site for covalent attachment of activated complement component C3. Mol. Immunol. 32: 711– 716.
44. Sim, R. B.,, T. M. Twose,, D. S. Patterson,, and E. Sim. 1981. The covalent-binding reaction of complement component C3. Biochem. J. 193: 115– 127.
45. Suchismita, R.,, K. Knox,, S. Segal,, D. Griffiths,, C. E. Moore,, K. I. Welsh,, A. Smarason,, N. P. Day,, W. I. McPheat,, D. W. Crook,, and A. V. S. Hill. 2002. MBL genotype and risk of invasive pneumococcal disease: a case-control study. Lancet 359: 1569– 1573.
46. Tack, B. F.,, R. A. Harrison,, J. Janatova,, M. L. Thomas,, and J. W. Prahl. 1980. Evidence for presence of an internal thiolester bond in third component of human complement. Proc. Natl. Acad. Sci. USA 77: 5764– 5768.
47. Tu, A.-H. T.,, R. L. Fulgham,, M. A. Mc-Crory,, D. E. Briles,, and A. J. Szalai. 1999. Pneumococcal surface protein A inhibits complement activation by Streptococcus pneumoniae. Infect. Immun. 67: 4720– 4724.
48. Ward, H. K.,, and J. F. Enders. 1933. An analysis of the opsonic and tropic action of normal and immune sera based on experiments with pneumococcus. J. Exp. Med. 57: 527– 547.
49. Weis, W. I.,, K. Drickhamer,, and W. A. Hendrickson. 1992. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature 360: 127– 134.
50. Wellmer, A.,, G. Zysk,, J. Gerber,, T. Kunst,, M. Von Mering,, S. Bunkowski,, H. Effert,, and R. Nau. 2002. Decreased virulence of a pneumolysin-deficient strain of Streptococcus pneumoniae in murine meningitis. Infect. Immun. 70: 6504– 6508.
51. Winkelstein, J. A.,, A. S. Abramovitz,, and A. Tomasz. 1980. Activation of C3 via the alternative complement pathway results in fixation of C3b to the pneumococcal cell wall. J. Immunol. 124: 2502– 2506.
52. Winkelstein, J. A.,, L. C. Cork,, D. E. Griffin,, R. J. Adams,, and D. L. Price. 1981. Genetically determined deficiency of the third component of complement in the dog. Science 212: 1169– 1173.
53. Winter, A. J.,, S. D. Comis,, M. P. Osborne,, M. J. Tarlow,, J. Stephen,, P. W. Andrew,, J. Hill,, and T. J. Mitchell. 1997. A role for pneumolysin but not neuraminidase in the hearing loss and cochlear damage induced by experimental pneumococcal meningitis in guinea pigs. Infect. Immun. 65: 4411– 4418.
54. Wright, A. E.,, and S. R. Douglas. 1903. An experimental investigation of blood fluids in connection with phagocytosis. Proc. R. Soc. Lond. B 72: 357– 370.
55. Xu, Y.,, M. Ma,, G. C. Ippolito,, H. W. Schroeder,, M. C. Carroll,, and J. E. Volanakis. 2001. Complement activation in factor D-deficient mice. Proc. Natl. Acad. Sci. USA 98: 14577– 14582.
56. Zhang, Y.,, A. W. Masi,, V. Barniak,, K. Mountzouros,, M. K. Hostetter,, and B. A. Green. 2001. Recombinant PhpA protein, a unique histidine motif-containing protein from Streptococcus pneumoniae, protects mice against intranasal pneumococcal challenge. Infect. Immun. 69: 3827– 3836.
57. Zipfel, P. F.,, C. Skerka,, J. Hellwage,, S. T. Jokiranta,, S. Meri,, V. Brade,, P. Kraiczy,, M. Noris,, and G. Remuzzi. 2002. Factor H family proteins: on complement, microbes, and human disease. Biochem. Soc. Trans. 30: 971– 978.

Tables

Interactions of Streptococcus pneumoniae with the Proteins of the Complement Pathways
[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/author/10.1128/9781555816537.chap13-1,webId=/content/author/10.1128/9781555816537.chap13-1,properties={foaf_givenname=Margaret K., foaf_name=Margaret K. Hostetter, foaf_surname=Hostetter, pub_isAffiliatedWith=[com.pub2web.rdf.cci.facet.ContentItem[id=http://asm.metastore.ingenta.com/content/affiliation/10.1128/9781555816537.chap13-aff1]]}]]
Citation: Hostetter M. 2004. Interactions of with the Proteins of the Complement Pathways, p 201-210. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch13
/content/10.1128/9781555816537.chap13.tab13-1
TABLE 1

Interactions of pneumococcal components with complement proteins

10.1128/9781555816537/tab13-1_thmb.gif
10.1128/9781555816537/tab13-1.gif
Generic image for table
TABLE 1

Interactions of pneumococcal components with complement proteins

Citation: Hostetter M. 2004. Interactions of with the Proteins of the Complement Pathways, p 201-210. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch13

Back to top
This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error