Dysregulation, Deficiency, and Virus Associated Pathologies Related to the Complement System

Abstract

The complement system is a frontline component of the immune response against invading pathogens. When functioning properly, it can help with the successful elimination of pathogens through opsonization, membrane attack complex formation, and cell signaling. When dysfunction or deficiency arises, these processes can be hindered and afflicted persons can be at increased risk of certain diseases due to the lack of complement protein production. These diseases can include systemic lupus erythematosus, glomerulonephritis, and increased risk of bacterial infections (de Cordoba et al., 2012). Several viruses have developed the capability of either evading or utilizing the complement system to their advantage. The emergence of SARS-CoV-2 has led to questions as to how this virus interacts with the complement system. While there is still much that is unknown, many of the pathologies caused by SARS-CoV-2 infection have a complement-induced component. For instance, patients diagnosed with severe COVID-19 disease have been noted to have elevated C3a and membrane attack complex components leading to lung, vasculature, and kidney damage (Java et al., 2020; Santiesteban-Lores et al., 2021). Additionally, the intracellular complement system, termed the complosome, is important for the regulation of immune cells by signaling homeostatic CD4+ T-cell survival through stimulating the mTOR pathway and for aiding in the immune response by activating the CD46 complement receptor (Liszewski et al., 2013; Arbore et al., 2017).