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Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis

Jarva, H; Ram, S; Vogel, U; Blom, Anna LU and Meri, S (2005) In Journal of Immunology 174(10). p.6299-6307
Abstract
Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor Cob-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus... (More)
Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor Cob-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C46p, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of Cob by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
174
issue
10
pages
6299 - 6307
publisher
American Association of Immunologists
external identifiers
  • wos:000228958900050
  • pmid:15879129
  • scopus:18644372663
ISSN
1550-6606
language
English
LU publication?
yes
id
f53b23dc-0d2b-4345-a100-6b29dd0e9df9 (old id 240499)
alternative location
http://www.jimmunol.org/cgi/content/full/174/10/6299
date added to LUP
2007-08-06 14:57:35
date last changed
2017-09-17 07:26:54
@article{f53b23dc-0d2b-4345-a100-6b29dd0e9df9,
  abstract     = {Neisseria meningitidis (meningococcus) is an important cause of meningitis and sepsis. Currently, there is no effective vaccine against serogroup B meningococcal infection. Host defense against neisseriae requires the complement system (C) as indicated by the fact that individuals deficient in properdin or late C components (C6-9) have an increased susceptibility to recurrent neisserial infections. Because the classical pathway (CP) is required to initiate efficient complement activation on neisseriae, meningococci should be able to evade it to cause disease. To test this hypothesis, we studied the interactions of meningococci with the major CP inhibitor Cob-binding protein (C4bp). We tested C4bp binding to wild-type group B meningococcus strain (H44/76) and to 11 isogenic mutants thereof that differed in capsule expression, lipo-oligosaccharide sialylation, and/or expression of either porin (Por) A or PorB3. All strains expressing PorA bound radiolabeled C46p, whereas the strains lacking PorA bound significantly less C4bp. Increased binding was observed under hypotonic conditions. Deleting PorB3 did not influence C4bp binding, but the presence of polysialic acid capsule reduced C4bp binding by 50%. Bound C4bp remained functionally active in that it promoted the inactivation of Cob by factor I. PorA-expressing strains were also more resistant to C lysis than PorA-negative strains in a serum bactericidal assay. Binding of C4bp thus helps Neisseria meningitidis to escape CP complement activation.},
  author       = {Jarva, H and Ram, S and Vogel, U and Blom, Anna and Meri, S},
  issn         = {1550-6606},
  language     = {eng},
  number       = {10},
  pages        = {6299--6307},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Binding of the complement inhibitor C4bp to serogroup B Neisseria meningitidis},
  volume       = {174},
  year         = {2005},
}