Staphylococcal complement inhibitor modulates phagocyte responses by dimerization of convertases

J Immunol. 2010 Jan 1;184(1):420-5. doi: 10.4049/jimmunol.0902865. Epub 2009 Nov 30.

Abstract

The human pathogen Staphylococcus aureus produces several complement-evasion molecules that enable the bacterium to withstand the host immune response. The human-specific staphylococcal complement inhibitor (SCIN) blocks the central C3 convertase enzymes that trigger critical complement functions, such as C3b deposition, phagocytosis, and C5a generation. SCIN effectively blocks the conversion of C3 by alternative pathway C3 convertases (C3bBb), but also induces dimerization of these enzymes. In this study, we show that formation of dimeric convertases by SCIN is important for S. aureus immune evasion because it modulates complement recognition by phagocytic receptors. Dimeric, but not monomeric, SCIN convertases showed an impaired binding to complement receptor 1 and the complement receptor of the Ig superfamily. The dimerization site of SCIN is essential for its strong antiphagocytic properties. These studies provide critical insights into the unique immune-evasion strategies used by S. aureus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • CHO Cells
  • Complement C3 / immunology
  • Complement C3 / metabolism
  • Complement C3-C5 Convertases / chemistry
  • Complement C3-C5 Convertases / immunology*
  • Complement C3-C5 Convertases / metabolism
  • Cricetinae
  • Cricetulus
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Phagocytosis / immunology*
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / metabolism
  • Staphylococcus aureus / immunology

Substances

  • Antigens, Bacterial
  • Complement C3
  • Staphylococcal decomplementation antigen
  • Complement C3-C5 Convertases