Complement: Bridging the innate and adaptive immune systems in sterile inflammation

• Published in: Journal of leukocyte biology Vol. 108; no. 1; pp. 339 - 351
• Main Authors: Lo, Martin W., Woodruff, Trent M.
• Format: Journal Article
• Language: English
• Published: United States 01-07-2020
• Subjects: alloimmunity; anaphylatoxins; C1q; cancer; hypertension; neuroinflammation; alloimmunity; C1q; cancer; neuroinflammation; hypertension; anaphylatoxins
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/JLB.3MIR0220-270R

The complement system is a collection of soluble and membrane‐bound proteins that together act as a powerful amplifier of the innate and adaptive immune systems. Although its role in infection is well established, complement is becoming increasingly recognized as a key contributor to sterile inflammation, a chronic inflammatory process often associated with noncommunicable diseases. In this context, damaged tissues release danger signals and trigger complement, which acts on a range of leukocytes to augment and bridge the innate and adaptive immune systems. Given the detrimental effect of chronic inflammation, the complement system is therefore well placed as an anti‐inflammatory drug target. In this review, we provide a general outline of the sterile activators, effectors, and targets of the complement system and a series of examples (i.e., hypertension, cancer, allograft transplant rejection, and neuroinflammation) that highlight complement's ability to bridge the 2 arms of the immune system.
Complement is a key actor at the innate and adaptive interface and, with a host of noncanonical capabilities, is an important determinant of sterile inflammation.