title: Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense.
abstract: As a preformed defense system, complement faces a delicate challenge in providing an immediate, forceful response to pathogens even at first encounter, while sparing host cells in the process. For this purpose, it engages a tightly regulated network of plasma proteins, cell surface receptors, and regulators. Complement component C3 plays a particularly versatile role in this process by keeping the cascade alert, acting as a point of convergence of activation pathways, fueling the amplification of the complement response, exerting direct effector functions, and helping to coordinate downstream immune responses. In recent years, it has become evident that nature engages the power of C3 not only to clear pathogens but also for a variety of homeostatic processes ranging from tissue regeneration and synapse pruning to clearing debris and controlling tumor cell progression. At the same time, its central position in immune surveillance makes C3 a target for microbial immune evasion and, if improperly engaged, a trigger point for various clinical conditions. In our review, we look at the versatile roles and evolutionary journey of C3, discuss new insights into the molecular basis for C3 function, provide examples of disease involvement, and summarize the emerging potential of C3 as a therapeutic target.
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. ricklin@upenn.edu.
authors: Daniel
authors: 0000-0001-6140-0233
authors: D
authors: Ricklin
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Edimara S
authors: ES
authors: Reis
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.|National Center for Scientific Research 'Demokritos', Athens, Greece.
authors: Dimitrios C
authors: DC
authors: Mastellos
authors: Utrecht University, Utrecht, The Netherlands.
authors: Piet
authors: 0000-0002-7782-2585
authors: P
authors: Gros
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA. lambris@upenn.edu.
authors: John D
authors: JD
authors: Lambris
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology*; D007113:Immunity, Innate; D007167:Immunotherapy / Q000639:trends*
chemical_list: D003176:Complement C3
keywords: compstatin; convertase; immune evasion; inflammation; therapeutics