The Role of Complement in Antibody Therapy for Infectious Diseases

The complement system is an integral and evolutionarily ancient component of the innate immune system, serving as the first line of defense against common pathogens (Fig. 1) (1). The prime functions of complement in innate host defense are accomplished through three effector pathways. These include lysis, inflammation, and opsonization (Fig. 2). The latter is central to microbial recognition and clearance by phagocytic cells. Complement further cooperates with Toll-like receptors in response to microbial structure and infection, in which immune responses are determined through both synergistic and antagonistic manners (1). Complement is also a functional bridge between innate and adaptive immunity, orchestrating an integrated host defense response to pathogenic challenges. For instance, complement can modulate adaptive immunity by providing signals that reinforce humoral responses to antigens by priming and regulating T cells and lowering the B-cell activation threshold (2, 3). It is also an important integral point for cross talk with other biological cascades to ensure homeostasis is maintained. One example is the interplay between the complement and coagulation cascades, whereby the complement system can amplify coagulation by enhancing local clotting and, as a result, preventing microbial spread through the systemic circulation. Likewise, the activated clotting factor XII can activate the classical complement pathway and thrombin can directly cleave the third and fifth complement components (C3 and C5, respectively) (4, 5).