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Impaired opsonization with C3b and phagocytosis of Streptococcus pneumoniae in sera from subjects with defects in the classical complement pathway

Yuste, Jose; Sen, Ashwin; Truedsson, Lennart LU ; Jönsson, Göran LU ; Tay, Liang-Seah; Hyams, Catherine; Baxendale, Helen E.; Goldblatt, Fiona; Botto, Marina and Brown, Jeremy S. (2008) In Infection and Immunity 76(8). p.3761-3770
Abstract
Results from studies using mice deficient in specific complement factors and clinical data on patients with an inherited deficiency of the classical complement pathway component C2 suggest that the classical pathway is vital for immunity to Streptococcus pneumoniae. However, the consequences of defects in classical pathway activity for opsonization with C3b and the phagocytosis of different S. pneumoniae serotypes in human serum are not known, and there has not been a systematic analysis of the abilities of sera from subjects with a C2 deficiency to opsonize S. pneumoniae. Hence, to investigate the role of the classical pathway in immunity to S. pneumoniae in more detail, How cytometry assays of opsonization with C3b and the phagocytosis... (More)
Results from studies using mice deficient in specific complement factors and clinical data on patients with an inherited deficiency of the classical complement pathway component C2 suggest that the classical pathway is vital for immunity to Streptococcus pneumoniae. However, the consequences of defects in classical pathway activity for opsonization with C3b and the phagocytosis of different S. pneumoniae serotypes in human serum are not known, and there has not been a systematic analysis of the abilities of sera from subjects with a C2 deficiency to opsonize S. pneumoniae. Hence, to investigate the role of the classical pathway in immunity to S. pneumoniae in more detail, How cytometry assays of opsonization with C3b and the phagocytosis of three capsular serotypes of S. pneumoniae were performed using human sera depleted of the complement factor C1q or B or sera obtained from C2-deficient subjects. The results demonstrate that, in human serum, the classical pathway is vital for C3b-iC3b deposition onto cells of all three serotypes of S. pneumoniae and seems to be more important than the alternative pathway for phagocytosis. Compared to the results for sera from normal subjects, C3b-iC3b deposition and total anti-S. pneumoniae antibody activity levels in sera obtained from C2(-/-) subjects were reduced and the efficiency of phagocytosis of all three S. pneumoniae strains was impaired. Anticapsular antibody levels did not correlate with phagocytosis or C3b-iC3b deposition. These data confirm that the classical pathway is vital for complement-mediated phagocytosis of S. pneumoniae and demonstrate why subjects with a C2 deficiency have a marked increase in susceptibility to S. pneumoniae infections. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Infection and Immunity
volume
76
issue
8
pages
3761 - 3770
publisher
American Society for Microbiology
external identifiers
  • wos:000258480900043
  • scopus:48849100792
  • pmid:18541650
ISSN
1098-5522
DOI
10.1128/IAI.00291-08
language
English
LU publication?
yes
id
1f838b11-2598-4aa6-b621-59f04b5bb6ac (old id 1252855)
date added to LUP
2008-11-03 12:15:25
date last changed
2017-10-01 03:58:34
@article{1f838b11-2598-4aa6-b621-59f04b5bb6ac,
  abstract     = {Results from studies using mice deficient in specific complement factors and clinical data on patients with an inherited deficiency of the classical complement pathway component C2 suggest that the classical pathway is vital for immunity to Streptococcus pneumoniae. However, the consequences of defects in classical pathway activity for opsonization with C3b and the phagocytosis of different S. pneumoniae serotypes in human serum are not known, and there has not been a systematic analysis of the abilities of sera from subjects with a C2 deficiency to opsonize S. pneumoniae. Hence, to investigate the role of the classical pathway in immunity to S. pneumoniae in more detail, How cytometry assays of opsonization with C3b and the phagocytosis of three capsular serotypes of S. pneumoniae were performed using human sera depleted of the complement factor C1q or B or sera obtained from C2-deficient subjects. The results demonstrate that, in human serum, the classical pathway is vital for C3b-iC3b deposition onto cells of all three serotypes of S. pneumoniae and seems to be more important than the alternative pathway for phagocytosis. Compared to the results for sera from normal subjects, C3b-iC3b deposition and total anti-S. pneumoniae antibody activity levels in sera obtained from C2(-/-) subjects were reduced and the efficiency of phagocytosis of all three S. pneumoniae strains was impaired. Anticapsular antibody levels did not correlate with phagocytosis or C3b-iC3b deposition. These data confirm that the classical pathway is vital for complement-mediated phagocytosis of S. pneumoniae and demonstrate why subjects with a C2 deficiency have a marked increase in susceptibility to S. pneumoniae infections.},
  author       = {Yuste, Jose and Sen, Ashwin and Truedsson, Lennart and Jönsson, Göran and Tay, Liang-Seah and Hyams, Catherine and Baxendale, Helen E. and Goldblatt, Fiona and Botto, Marina and Brown, Jeremy S.},
  issn         = {1098-5522},
  language     = {eng},
  number       = {8},
  pages        = {3761--3770},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Impaired opsonization with C3b and phagocytosis of Streptococcus pneumoniae in sera from subjects with defects in the classical complement pathway},
  url          = {http://dx.doi.org/10.1128/IAI.00291-08},
  volume       = {76},
  year         = {2008},
}