Present address: Department of Medical Microbiology and Infection Prevention, VU Medical Center, Amsterdam, 1081 BT, The Netherlands.
Functional basis for complement evasion by staphylococcal superantigen-like 7
Article first published online: 25 MAY 2010
© 2010 Blackwell Publishing Ltd
Volume 12, Issue 10, pages 1506–1516, October 2010
How to Cite
Bestebroer, J., Aerts, P. C., Rooijakkers, S. H. M., Pandey, M. K., Köhl, J., Van Strijp, J. A. G. and De Haas, C. J. C. (2010), Functional basis for complement evasion by staphylococcal superantigen-like 7. Cellular Microbiology, 12: 1506–1516. doi: 10.1111/j.1462-5822.2010.01486.x
- Issue published online: 7 SEP 2010
- Article first published online: 25 MAY 2010
- Received 9 September, 2009; revised 15 April, 2010; accepted 11 May, 2010.
The human pathogen Staphylococcus aureus has a plethora of virulence factors that promote its colonization and survival in the host. Among such immune modulators are staphylococcal superantigen-like (SSL) proteins, comprising a family of 14 small, secreted molecules that seem to interfere with the host innate immune system. SSL7 has been described to bind immunoglobulin A (IgA) and complement C5, thereby inhibiting IgA-FcαRI binding and serum killing of Escherichia coli. As C5a generation, in contrast to C5b-9-mediated lysis, is crucial for immune defence against staphylococci, we investigated the impact of SSL7 on staphylococcal-induced C5a-mediated effects. Here, we show that SSL7 inhibits C5a generation induced by staphylococcal opsonization, slightly enhanced by its IgA-binding capacity. Moreover, we demonstrate a strong protective activity of SSL7 against staphylococcal clearance in human whole blood. SSL7 strongly inhibited the C5a-induced phagocytosis of S. aureus and oxidative burst in an in vitro whole-blood inflammation model. Furthermore, we found that SSL7 affects all three pathways of complement activation and inhibits the cleavage of C5 by interference of its binding to C5 convertases. Finally, SSL7 effects were also demonstrated in vivo. In a murine model of immune complex peritonitis, SSL7 abrogated the C5a-driven influx of neutrophils in mouse peritoneum.