Abstract

The complement system is an evolutionarily conserved arm of innate immunity, which forms one of the first lines of host response to pathogens and assists in the clearance of debris. A deficiency in key activators/amplifiers of the cascade results in recurrent infection, whereas a deficiency in regulating the cascade predisposes to accelerated organ failure, as observed in colitis and transplant rejection. Given that there are over 60 proteins in this system, it has become an attractive target for immunotherapeutics, many of which are United States Food and Drug Administration-approved or in multiple phase 2/3 clinical trials. Moreover, there have been key advances in the last few years in the understanding of how the complement system operates locally in tissues, independent of its activities in circulation. In this review, we will put into perspective the abovementioned discoveries to optimally modulate the spatiotemporal nature of complement activation and regulation at mucosal surfaces.

MeSH

Transplantation, Infections, Pneumonia, Complement System Proteins, Immunity, Mucosal, Complement Activation, Colitis, Sars-Cov-2

Cited by

• Impaired complement regulation drives chronic lung allograft dysfunction after lung transplantation. bioRxiv, 2024
• mSphere of Influence: Complement activity beyond systemic circulation-implications in the context of infections. mSphere, 2025
• The C3-C3aR axis modulates trained immunity in alveolar macrophages. bioRxiv, 2024
• The Establishment of Complement System Is from Gene Duplication and Domain Shuffling. Int J Mol Sci, 2024