Returning the Complement

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Science  26 Aug 2005:
Vol. 309, Issue 5739, pp. 1302
DOI: 10.1126/science.309.5739.1302d

Many an immunology undergraduate's headache can be traced to memorizing the intricacies of the complement system. Three activation pathways lead to the generation of the C3 converting enzymes, which are responsible for generating the effector molecules that carry out crucial host defence functions. As a result, the complement system is a target for viral and bacterial evasion strategies.

The bacterial pathogen Staphylococcus aureus has evolved a bacteriophage-encoded pathogenicity gene cluster (SaP15) that is present in 90% of strains and encodes four secreted human-specific virulence proteins. Rooijakkers et al.observed that one of these, designated SCIN, inhibited bacterial phagocytosis by human neutrophils, by blocking the deposition of the complement factor C3b on bacterial membranes, which is a crucial step in opsonization. Further upstream, SCIN could inhibit all three pathways by binding to the C3 convertases (C4b2a and C3bBb). Potentially, such interactions could alter the intrinsic decay potential of the convertases, which activate downstream effector molecules of the complement pathway. As a consequence, SCIN has the ability to interfere with the complement system at multiple points, making it a drug development target for diseases involving aberrant complement activity. — SJS

Nat.Immunol. 10.1038/ni1235 (2005).

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