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Clinical isolates of Streptococcus pneumoniae bind the complement inhibitor C4b-binding protein in a PspC allele-dependent fashion.

Dieudonné-Vatran, Antoine; Krentz, Stefanie; Blom, Anna LU ; Meri, Seppo; Henriques-Normark, Birgitta; Riesbeck, Kristian LU and Albiger, Barbara LU (2009) In Journal of Immunology 182(12). p.7865-7877
Abstract
The complement system constitutes an important component of the innate immune system. To colonize their host and/or to cause disease, many pathogens have evolved strategies to avoid complement-mediated bacterial lysis and opsonophagocytosis. In this study, using a collection of 55 clinical isolates of Streptococcus pneumoniae, we demonstrate for the first time that pneumococci bind the complement inhibitor C4b-binding protein (C4BP). C4BP binding seems to be restricted to certain serotypes such as serotype 4, 6B, 7F, and 14, of which the strains of serotype 14 are the strongest binders. We show that bacteria-bound C4BP retains its functional activity and down-regulates the activation of the classical pathway. Thus, this major respiratory... (More)
The complement system constitutes an important component of the innate immune system. To colonize their host and/or to cause disease, many pathogens have evolved strategies to avoid complement-mediated bacterial lysis and opsonophagocytosis. In this study, using a collection of 55 clinical isolates of Streptococcus pneumoniae, we demonstrate for the first time that pneumococci bind the complement inhibitor C4b-binding protein (C4BP). C4BP binding seems to be restricted to certain serotypes such as serotype 4, 6B, 7F, and 14, of which the strains of serotype 14 are the strongest binders. We show that bacteria-bound C4BP retains its functional activity and down-regulates the activation of the classical pathway. Thus, this major respiratory pathogen may escape immune recognition and eradication by the complement system. Furthermore, we show that C4BP binding varies between strains but is dependent on the expression of pneumococcal surface protein C, PspC of group 4. The study of the distribution of group 4 pspC locus shows that most of high-binder serotype 14 isolates harbor an allelic variant of group 4 pspC. Using PspC-negative mutant strains, we identified a new allelic variant of PspC (PspC4.4) as a major ligand for C4BP, revealing a new function for this important pneumococcal virulence factor. Thus pneumococci exploit host C4BP for complement evasion in a PspC allele-dependent manner. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bacterial Proteins: metabolism, Bacterial Proteins: genetics, Bacterial Proteins: immunology, Complement C4b-Binding Protein: genetics, Complement C4b-Binding Protein: immunology, Complement C4b-Binding Protein: metabolism, Mutation: genetics, Streptococcus pneumoniae: genetics, Streptococcus pneumoniae: immunology, Streptococcus pneumoniae: metabolism, Streptococcus pneumoniae: isolation & purification
in
Journal of Immunology
volume
182
issue
12
pages
7865 - 7877
publisher
American Association of Immunologists
external identifiers
  • WOS:000266833900058
  • PMID:19494311
  • Scopus:67649201006
ISSN
1550-6606
DOI
10.4049/jimmunol.0802376
language
English
LU publication?
yes
id
d9a45d20-168e-4488-839f-bbd6c425a7db (old id 1434529)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19494311?dopt=Abstract
date added to LUP
2009-07-03 13:34:13
date last changed
2017-01-22 04:17:56
@article{d9a45d20-168e-4488-839f-bbd6c425a7db,
  abstract     = {The complement system constitutes an important component of the innate immune system. To colonize their host and/or to cause disease, many pathogens have evolved strategies to avoid complement-mediated bacterial lysis and opsonophagocytosis. In this study, using a collection of 55 clinical isolates of Streptococcus pneumoniae, we demonstrate for the first time that pneumococci bind the complement inhibitor C4b-binding protein (C4BP). C4BP binding seems to be restricted to certain serotypes such as serotype 4, 6B, 7F, and 14, of which the strains of serotype 14 are the strongest binders. We show that bacteria-bound C4BP retains its functional activity and down-regulates the activation of the classical pathway. Thus, this major respiratory pathogen may escape immune recognition and eradication by the complement system. Furthermore, we show that C4BP binding varies between strains but is dependent on the expression of pneumococcal surface protein C, PspC of group 4. The study of the distribution of group 4 pspC locus shows that most of high-binder serotype 14 isolates harbor an allelic variant of group 4 pspC. Using PspC-negative mutant strains, we identified a new allelic variant of PspC (PspC4.4) as a major ligand for C4BP, revealing a new function for this important pneumococcal virulence factor. Thus pneumococci exploit host C4BP for complement evasion in a PspC allele-dependent manner.},
  author       = {Dieudonné-Vatran, Antoine and Krentz, Stefanie and Blom, Anna and Meri, Seppo and Henriques-Normark, Birgitta and Riesbeck, Kristian and Albiger, Barbara},
  issn         = {1550-6606},
  keyword      = {Bacterial Proteins: metabolism,Bacterial Proteins: genetics,Bacterial Proteins: immunology,Complement C4b-Binding Protein: genetics,Complement C4b-Binding Protein: immunology,Complement C4b-Binding Protein: metabolism,Mutation: genetics,Streptococcus pneumoniae: genetics,Streptococcus pneumoniae: immunology,Streptococcus pneumoniae: metabolism,Streptococcus pneumoniae: isolation & purification},
  language     = {eng},
  number       = {12},
  pages        = {7865--7877},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Clinical isolates of Streptococcus pneumoniae bind the complement inhibitor C4b-binding protein in a PspC allele-dependent fashion.},
  url          = {http://dx.doi.org/10.4049/jimmunol.0802376},
  volume       = {182},
  year         = {2009},
}