The effects of PspC on complement-mediated immunity to Streptococcus pneumoniae vary with strain background and capsular serotype.
Streptococcus pneumoniae may evade complement activity by binding of factor H (FH), a negative regulator of the alternative pathway, to the surface protein PspC. However, existing data on the effects of FH binding to PspC on complement activity are conflicting, and there is also considerable allelic variation in PspC structure between S. pneumoniae strains that may influence PspC-dependent effects on complement. We have investigated interactions with complement for several S. pneumoniae strains in which the gene encoding PspC has been deleted. The degree of FH binding varied between strains and was entirely dependent on PspC for seven strains. Data obtained with TIGR4 strains expressing different capsular serotypes suggest that FH binding is affected by capsular serotype. Results of immunoblot analysis for C3 degradation products and iC3b deposition assays suggested that FH bound to PspC retained functional activity, but loss of PspC had strikingly varied effects on C3b/iC3b deposition on S. pneumoniae, with large increases on serotype 4, 6A, 6B, and 9V strains but only small increases or even decreases on serotype 2, 3, 17, and 23F strains. Repeating C3b/iC3b assays with TIGR4 strains expressing different capsular serotypes suggested that differences in the effect of PspC on C3b/iC3b deposition were largely independent of capsular serotype and depend on strain background. However, data obtained from infection in complement-deficient mice demonstrated that differences between strains in the effects of PspC on complement surprisingly did not influence the development of septicemia.
Yuste
Jose
J
Centre for Respiratory Research, Department of Medicine, Royal Free and University College Medical School, Rayne Institute, London WC1E 6JJ, United Kingdom.
Khandavilli
Suneeta
S
Ansari
Naadir
N
Muttardi
Kairya
K
Ismail
Laura
L
Hyams
C
C
Weiser
Jeffrey
J
Mitchell
Timothy
T
Brown
Jeremy S
JS
D000818:Animals; D016667:Bacterial Capsules; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D003167:Complement Activation / Q000502:physiology*; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence
D001426:Bacterial Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D003165:Complement System Proteins