Human complement control and complement evasion by pathogenic microbes--tipping the balance

Complement is a central homeotic system of mammals and represents the first defense line of innate immunity. The human complement system is aimed to maintain homeostasis by recognizing and removing damaged or modified self material, as well as infectious foreign microbes. However, pathogenic microbes also control and escape the host complement and immune attack. The increasing resistance of microbial pathogens to either antibiotics or antifungal drugs is a major health problem and is of global interest. Therefore the topic how pathogenic microbes escape human complement and immune control is of high and of central interest. Identifying and defining the action of proteins involved in this intense immune interaction and understanding how these proteins interact is of relevance to design new control strategies. In this review we summarize the complement system of the human host and how this cascade drives effector functions. In addition, we summarize how diverse pathogenic microbes control, modulate and block the complement response of their host. The characterization of pathogen derived virulence factors and complement escape proteins reveals patterns of multiplicity, diversity and redundancy among pathogen encoded proteins. Sequence variability of immune and also complement escape proteins is largely driven by antigenic diversity and adaptive immunity. However common complement escape principles are, emerging in terms of conserved binding repertoire for host regulators and evasion among the large variety of infectious microbes. These conserved and common escape features are relevant and they provide challenging options for new therapeutic approaches.