Guianensin, a Blackfly Salivary Protein, Inhibits the Lectin Pathway of Complement

Salivary secretions from blood-feeding arthropods are rich in bioactive compounds that counteract blood clotting, platelet aggregation, complement activation, and vasoconstriction. Despite the identification and characterization of various salivary components in blood-feeding arthropods, their role in complement inhibition, particularly in black flies, remains underexplored. Here, we found that Guianensin, a salivary protein from Simulium guianense, is a specific inhibitor of the lectin pathway of the complement. Guianensin targets MASP-2, a serine protease crucial for LP activation resulting in reduced C4 and C5b-9 complex deposition. Guianensin also inhibits the procoagulant activity of MASP-2 in vitro. No interaction with C1s, C1r, or other downstream complement proteins was found. Using a lipopolysaccharide-induced murine lung injury model, Guianensin significantly reduced neutrophil numbers and inflammatory cytokines, demonstrating its strong anti-inflammatory activity in vivo. Guianensin emerges as a novel complement inhibitor and a potential candidate for therapeutic applications.