The grand escape – how pathogens outsmart the human complement system

Infectious diseases remain a significant cause of mortality and morbidity worldwide. Complement is a critical component in the defense against pathogens and despite their great differences, viruses, bacteria, fungi, and protists have all developed similar mechanisms of evasion from the human complement system. Using examples from four microbial groups (viruses, bacteria, fungi and protists), this review expands on examples of these different mechanisms of evasion. The mechanisms are grouped as (A) avoidance of recognition, (B) avoidance of eradication, (C) avoidance of activation and function, or (D) use of the complement proteins for entry into the host, in accordance with the classification initially proposed in 1999. Furthermore, this review will expand on novel descriptions of complement evasion, for example involving intracellular complement. Taken toge complement evasion is an essential tool used by pathogens not only in a defensive manner, protecting the pathogen from the host, but can also employed in an aggressive manner to aid the invasion of the host. Understanding these mechanisms has already influenced diagnostic and therapeutic tools, including vaccine development, and a further expansion of evasion molecules as biomarkers, vaccines or targets for therapy appears likely in the future.