Effects of Streptococcus pneumoniae strain background on complement resistance.
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.


RESULTS
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.
Centre for Respiratory Research, Department of Medicine, University College Medical School, Rayne Institute, London, United Kingdom.
Catherine
C
Hyams
Sophia
S
Opel
William
W
Hanage
Jose
J
Yuste
Katie
K
Bax
Birgitta
B
Henriques-Normark
Brian G
BG
Spratt
Jeremy S
JS
Brown
D000907:Antibodies, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D015922:Complement C1q / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011485:Protein Binding; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000276:immunology* / Q000302:isolation & purification
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D015922:Complement C1q; D003165:Complement System Proteins