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

Nature Immunology volume 6, pages 920–927 (2005)Cite this article

Abstract

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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Figure 1: SCIN inhibits phagocytosis and killing of S. aureus by interfering with human complement.
Figure 2: SCIN inhibits all three complement pathways.
Figure 3: SCIN is a human-specific complement inhibitor.
Figure 4: SCIN binds to particles in a serum- and temperature-dependent way.
Figure 5: SCIN interferes with formation of C3 convertases.
Figure 6: SCIN prevents the dissociation of C3 convertases.
Figure 7: SCIN binds and inactivates C3bBb.

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Acknowledgements

We thank W. Jansen for reviewing the manuscript, and L. de Graaf-Miltenburg for purification of factor B and C3. Supported by the European Union (LSHM-CT-2004-512093 and QLG1-CT-2001-01039).

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Authors and Affiliations

  1. Eijkman Winkler Institute, University Medical Center Utrecht, G04.614, Utrecht, 3584, CX, The Netherlands

    Suzan H M Rooijakkers, Maartje Ruyken, Willem J B van Wamel, Kok P M van Kessel & Jos A G van Strijp

  2. Department of Nephrology, C3P, Leiden University Medical Center, Leiden, 2300, RC, The Netherlands

    Anja Roos & Mohamed R Daha

  3. Department of Biochemistry, Medical Research Council Immunochemistry Unit, University of Oxford, Oxford, OX1 3QU, UK

    Julia S Presanis & Robert B Sim

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  1. Suzan H M Rooijakkers
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Correspondence to Suzan H M Rooijakkers.

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Supplementary information

Supplementary Fig. 1

Specificity of anti-SCIN antibodies. (PDF 92 kb)

Supplementary Fig. 2

SCIN interferes with formation and proteolytic activity of C3 convertases. (PDF 99 kb)

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Rooijakkers, S., Ruyken, M., Roos, A. et al. Immune evasion by a staphylococcal complement inhibitor that acts on C3 convertases. Nat Immunol 6, 920–927 (2005). https://doi.org/10.1038/ni1235

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