The role of clip-domain serine protease homologs in A. gambiae immune responses to systemic infections -

Abstract

Malaria is one of the most devastating mosquito-borne infectious diseases of humans in the tropical and subtropical regions. It is caused by parasites of the genus Plasmodium which develop through several stages inside the mosquito vector before being transmitted into the human host. Functional genetic studies in A. gambiae, the major malaria vector in Sub-Saharan Africa, where mortalities from malaria are the highest, showed that the mosquito is not a passive vector for the parasite; rather, the parasite suffers dramatic reduction in numbers in its transitional development from the ookinete to the oocyst stage. These losses have been largely attributed to the mosquito immune response, and several immunity genes involved in that process have been identified. Initial efforts to study mosquito immunity were directed towards the malaria parasite, being an important pathogen to mankind. However, the fact that several immune effector responses that efficiently kill Plasmodium parasites, particularly in the ookinete stages, were are also found to be effective against bacteria, and that the midgut microbiota of the mosquito has significant impact on the survival of parasites, broadened the spectrum of microorganisms used in mosquito immunity studies. The general belief that emerged from these studies collectively is that bacteria and fungi constitute most likely the main pressure on the mosquito immune system in the field rather than malaria parasites which are carried by a small percentage of mosquitoes that do not exceed 2percent in endemic regions during peak seasons of transmission. Hence, the use of bacteria and fungi as model pathogens in mosquito immunity studies offer several advantages: First, these microorganisms are more tractable than malaria parasites in several aspects which help deciphering certain immune mechanisms at the molecular level in a manner that would not be possible using the parasite. Second, they might be more relevant than malaria parasites to the understanding of mosquito immunity since bacteria