The complement system is a major component of innate immunity and consists of both soluble factors and cell surface receptors that interact to sense and respond to invading pathogens. The complement system links the innate and adaptive immune responses by a variety of mechanisms including enhancing humoral immunity, regulating antibody effector mechanisms, and modulating T cell function. In addition to these roles in normal host immune responses, the complement system has pathogenic roles in a variety of ischemic, inflammatory, and autoimmune diseases.
The complement system is a critical determinant of the outcome of infection by a variety of different viruses. Our understanding of the mechanisms by which complement protects from virus-induced disease has improved dramatically. Research in this area will not only continue to contribute to our knowledge of viral pathogenesis, but will continue to provide insight into the regulation of immune responses, and lead to improved therapeutic and vaccine approaches for both viral and non-viral pathogens. Perhaps less well understood are the mechanisms by which complement functions as a pathogenic effector in some virus-induced diseases. Further progress towards identifying the signals and pathways that lead to complement activation, which are not understood for many viruses, particularly in vivo, and a deeper understanding of the impact of complement activation on host immune responses to viral infection may shed light. Continued investigation of the role of complement in viral pathogenesis will provide important insights into virus–host interactions and strategies to prevent or treat virus-induced disease.
Complement and viral pathogenesis. Virology. 2011 411(2): 362-373
The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection.