Guianensin, a blackfly salivary protein, inhibits the lectin pathway of complement 9038

Abstract Description 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. In this study, we found that Guianensin, a salivary protein from Simulium guianense, is a specific inhibitor of the lectin pathway (LP) of complement. Guianensin belongs to the Kunitz domain of protease inhibitors and targets various serine proteases involved in hemostasis and inflammation, including MASP-2, a serine protease crucial for LP activation resulting in reduced C4 and C5b-9 complex deposition. Guianensin also inhibits the procoagulant activity MASP-2 in vitro. Surface plasmon resonance analysis confirmed its specific binding to MASP-2, with high affinity. No interaction with C1s, C1r, or other downstream complement proteins was found. These results underscore the potential of Guianensin for investigating the role of the complement inhibition in blood feeding and pathogen transmission by Simulium spp., offering new insights into the adaptive functions of salivary components in these vectors. Guianensin emerges as a novel complement inhibitor and a possible candidate for therapeutic applications. Funding Sources This research was supported by the Division of Intramural Research Program of the NIH/NIAID (AI001246) Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)