Malaria infects as many half a billion people every year and kills between 1 and 3 million people annually, many of them children living in sub-Saharan Africa. It is caused by Plasmodium spp. protozoans transmitted between humans and mosquitoes via the blood. When a mosquito consumes infected human blood, its immune system attacks Plasmodium and kills roughly 80–90% of the parasites, but the surviving parasites multiply and are then transmitted to other humans by mosquito bites, spreading the disease. A recent study has elucidated the mechanism by which the mosquito's immune system responds to Plasmodium. The results raise the possibility that we could learn to enhance this immune response, enabling mosquitoes to eliminate Plasmodium more effectively and minimizing malaria transmission from mosquitoes to humans.

The study, led by George K. Christophides and colleagues (Imperial College London, UK), focused on Anopheles gambiae mosquitoes infected with Plasmodium berghei, a species that causes malaria in rodents but not in humans. Christophides' group identified two proteins, called LRIM1 and APL1C, that seem to mediate the mosquitoes' immune attack on P. berghei (Science, published online 5 March 2009; doi:10.1126/science.1171400). LRIM1 and APL1C form a complex that is secreted into the hemolymph, where it interacts with a third protein called TEP1. The LRIM1–APL1C complex may process TEP1 into an active form or help stabilize it in the hemolymph. TEP1 then binds to P. berghei parasites and kills them. The nature of the interaction between TEP1 and the LRIM1–APL1C complex warrants further investigation. More studies are also needed to determine how some Plasmodium parasites escape the mosquitoes' immune response.

LRIM1 and APL1C proteins contain repeating amino acid sequences that are rich in leucine. Such leucine-rich repeat–containing (LRR) proteins are important in host defense in both plants and animals. LRIM1 and APL1C belong to a family of LLR proteins that seems to be specific to mosquitoes; proteins with similar structural features have been found in mosquito vectors of other infectious diseases (such as Aedes egyptii, which can transmit yellow and dengue fevers, and Culex quinquefasciatus, which can transmit filariasis) but not in any other species. Christophides and his fellow researchers are investigating whether mosquito-specific LRR proteins are involved in immune responses to these infections as well. If they are, the results of the future studies could have implications for controlling various dangerous human pathogens.