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