Complement C3 as a target of host modulation in periodontitis

Abstract

Although originally identified as a blood-based antimicrobial system, complement is now regarded as a central regulator of immune and inflammatory responses and tissue homeostasis. When dysregulated or overactivated, however, complement can turn from a homeostatic to a pathological effector that drives a number of inflammatory disorders. In this context, destructive periodontal inflammation in humans is correlated with elevated complement activity. Moreover, mechanistic studies in mice have causally linked the central complement component C3 and downstream signaling pathways in the induction of periodontal dysbiosis and inflammation that leads to alveolar bone loss. Consistent with this, pharmacological inhibition of C3 activation by a locally administered drug (Cp40/AMY-101) was shown to suppress both induced and naturally occurring periodontitis in non-human primates. Thus, C3-targeted intervention represents a promising host-modulation approach to treat human periodontitis.