Hyams, C;
Opel, S;
Hanage, W;
Yuste, J;
Bax, K;
Henriques-Normark, B;
Spratt, BG;
(2011)
Effects of Streptococcus pneumoniae Strain Background on Complement Resistance.
PLOS ONE
, 6
(10)
, Article e24581. 10.1371/journal.pone.0024581.
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Abstract
Background: Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive infections. Although capsular serotype is one important factor causing differences in complement resistance between strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complement-mediated immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same capsular serotype vary in their sensitivity to complement mediated immunity.Methodology and Principal Findings: C3b/iC3b deposition and neutrophil association were measured using flow cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS.Conclusions: These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the differences in virulence between strains.
| Type: | Article |
|---|---|
| Title: | Effects of Streptococcus pneumoniae Strain Background on Complement Resistance |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0024581 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0024581 |
| Language: | English |
| Additional information: | © 2011 Hyams et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was undertaken at University College London, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme. CH was supported by the Astor Foundation and Glaxo Smith Kline through the University College London MB PhD programme. JY was supported by the British Lung Foundation (P05/3). BHN is supported by the Ragnar and Torsten Söderberg foundation and the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | HISTIDINE TRIAD PROTEINS, CAPSULAR SEROTYPE, MEDIATED IMMUNITY, INVASIVE-DISEASE, INNATE IMMUNITY, PHASE VARIATION, MOSAIC GENES, FACTOR-H, DEPOSITION, INFECTION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1325605 |
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