A genetic study of Plasmodium susceptibility in the African malaria vector Anopheles gambiae.

We are studying the interaction between malarial parasites and their mosquito hosts by a process based on the genetic selection of lines of the mosquito vector that will not support normal parasite development. The model system we are using is the mosquito Anopheles gambiae and a number of different human and non-human primate malarial parasites. Our first effort in this general approach involved the selection of a strain of An. gambiae that was able to encapsulate the malarial parasite during or just after its penetration of the mosquito midgut. This mosquito has been found to be highly refractory to a wide variety of different Plasmodium species and at least partially refractory to all four human malarial parasites. The basis of this phenomenon appears to be the mosquito's enhanced ability to mount a normal encapsulation response against invading pathogens or parasites. The late ookinete is enclosed in a heavily melanized capsule approximately 16-24 hours after the mosquito takes an infective blood meal. Encapsulation appears to be primarily humoral; electron microscopy reveals evidence of the phenomenon as the ookinete passes through or between midgut cells, and no hemocyte involvement has been observed. Subcellular structures in newly encapsulated parasites appear normal, indicating that live rather than dead or dying parasites are encapsulated. Preliminary studies suggest that two unlinked loci contribute to the refractory mosquito phenotype. One of these loci is very closely linked to a region of the mosquito genome that includes two esterases.(ABSTRACT TRUNCATED AT 250 WORDS)