Pneumococcal surface protein A inhibits complement deposition on the pneumococcal surface by competing with the binding of C-reactive protein to cell-surface phosphocholine

Academic Article


  • In the presence of normal serum, complement component C3 is deposited on pneumococci primarily via the classical pathway. Pneumococcal surface protein A (PspA), a major virulence factor of pneumococci, effectively inhibits C3 deposition. PspA'sC terminus has a choline-binding domain that anchors PspA to the phosphocholine (PC)moieties on the pneumococcal surface. C-reactive protein (CRP), another important host defense molecule, also binds to PC, and CRP binding to pneumococci enhances complement C3 deposition through the classical pathway. Using flow cytometry of PspA and PspA strains, we observed that the absence of PspA led to exposure of PC, enhanced the surface binding ofCRP, and increased the deposition of C3.Moreover, when the PspA mutant was incubated with a pneumococcal eluate containing native PspA, there was decreased deposition of CRP and C3 on the pneumococcal surface compared with incubation with an eluate from a PspA strain. This inhibition was not observed when a recombinant PspA fragment, which lacks the choline-binding region of PspA, was added to the PspA mutant. Also, there was much greater C3 deposition onto the PspA pneumococcus when exposed to normal mouse serum from wild-type mice as compared with that from CRP knockout mice. Furthermore, when CRP knockout mouse serum was replenished with CRP, there was a dose-dependent increase in C3 deposition. The combined data reveal a novel mechanism of complement inhibition by a bacterial protein: inhibition of CRP surface binding and, thus, diminution of CRP-mediated complement deposition. Copyright©2012 by The American Association of Immunologists, Inc. + - - - - -
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    Author List

  • Mukerji R; Mirza S; Roche AM; Widener RW; Croney CM; Rhee DK; Weiser JN; Szalai AJ; Briles DE
  • Start Page

  • 5327
  • End Page

  • 5335
  • Volume

  • 189
  • Issue

  • 11