title: Staphylococcal complement inhibitor modulates phagocyte responses by dimerization of convertases.
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.
authors: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. i.jongerius@umcutrecht.nl
authors: Ilse
authors: I
authors: Jongerius
authors: Manon
authors: M
authors: Puister
authors: Jin
authors: J
authors: Wu
authors: Maartje
authors: M
authors: Ruyken
authors: Jos A G
authors: JA
authors: van Strijp
authors: Suzan H M
authors: SH
authors: Rooijakkers
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D050577:Complement C3-C5 Convertases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010587:Phagocytosis / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D003176:Complement C3; C044100:Staphylococcal decomplementation antigen; D050577:Complement C3-C5 Convertases