Leucine-Rich Repeat Protein Complex Activates Mosquito Complement in Defense Against Plasmodium Parasites

Abstract

Leucine-rich repeat–containing proteins are central to host defense in plants and animals. We show that in the mosquito Anopheles gambiae , two such proteins that antagonize malaria parasite infections, LRIM1 and APL1C, circulate in the hemolymph as a high-molecular-weight complex held together by disulfide bridges. The complex interacts with the complement C3-like protein, TEP1, promoting its cleavage or stabilization and its subsequent localization on the surface of midgut-invading Plasmodium berghei parasites, targeting them for destruction. LRIM1 and APL1C are members of a protein family with orthologs in other disease vector mosquitoes and appear to be important effectors in innate mosquito defenses against human pathogens.