Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases

• Published in: Nature Immunology 2005-09, Vol.6 (9), p.920-927
• Main Authors: Rooijakkers, Suzan H M, Ruyken, Maartje, Roos, Anja, Daha, Mohamed R, Presanis, Julia S, Sim, Robert B, van Wamel, Willem J B, van Kessel, Kok P M, van Strijp, Jos A G
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - immunology; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Biomedicine; Complement C3 Convertase, Alternative Pathway; Complement C3b - metabolism; Complement Inactivator Proteins - immunology; Complement Inactivator Proteins - metabolism; Complement System Proteins - immunology; Complement System Proteins - metabolism; Humans; Immunology; Infectious Diseases; Neutrophils - immunology; Peptide Fragments - metabolism; Phagocytosis; Staphylococcus aureus; Staphylococcus aureus - immunology; Staphylococcus aureus - metabolism
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1235

The complement system is pivotal in host defense but also contributes to tissue injury in several diseases. The assembly of C3 convertases (C4b2a and C3bBb) is a prerequisite for complement activation. The convertases catalyze C3b deposition on activator surfaces. Here we describe the identification of staphylococcal complement inhibitor, an excreted 9.8-kilodalton protein that blocks human complement by specific interaction with C4b2a and C3bBb. Staphylococcal complement inhibitor bound and stabilized C3 convertases, interfering with additional C3b deposition through the classical, lectin and alternative complement pathways. This led to a substantial decrease in phagocytosis and killing of Staphylococcus aureus by human neutrophils. As a highly active and small soluble protein that acts exclusively on surfaces, staphylococcal complement inhibitor may represent a promising anti-inflammatory molecule.