Nature Immunology
6, 920 - 927 (2005)
Published online: 7 August 2005; | doi:10.1038/ni1235
Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertasesSuzan H M Rooijakkers1, Maartje Ruyken1, Anja Roos2, Mohamed R Daha2, Julia S Presanis3, Robert B Sim3, Willem J B van Wamel1, Kok P M van Kessel1
& Jos A G van Strijp11
Eijkman Winkler Institute, University Medical Center Utrecht, G04.614, 3584 CX Utrecht, The Netherlands. 2
Department of Nephrology, C3P, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. 3
Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
Correspondence should be addressed to Suzan H M Rooijakkers s.h.m.rooijakkers@azu.nl 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.
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