Interaction between host complement and mosquito-midgut-stage Plasmodium berghei

After ingestion by mosquitoes, gametocytes of malaria parasites become acti vated and form extracellular gametes that are no longer protected by the re d blood cell membrane against immune effectors of host blood. We have studi ed the action of complement on Plasmodium developmental stages in the mosqu ito blood meal using the rodent malaria parasite Plasmodium berghei and rat complement as a model. We have shown that in the mosquito midgut, rat comp lement components necessary to initiate the alternative pathway (factor B, factor D, and C3) as well as C5 are present for several hours following ing estion of P. berghei-infected rat blood. In culture, 30 to 50% of mosquito midgut stages of P. berghei survived complement exposure during the first 3 h of development. Subsequently, parasites became increasingly sensitive to complement lysis. To investigate the mechanisms involved in their protecti on, we tested for C3 deposition on parasite surfaces and whether host CD59 (a potent inhibitor of the complement membrane attack complex present on re d blood cells) was taken up by gametes while emerging from the host cell. B etween 0.5 and 22 h, 90% of Pbs21-positive parasites were positive for C3. While rat red and white blood cells stained positive for CD59, Pbs21-positi ve parasites were negative for CD59. In addition, exposure of parasites to rat complement in the presence of anti-rat CD59 antibodies did not increase lysis. These data suggest that parasite or host molecules other than CD59 are responsible for the protection of malaria parasites against complement- mediated lysis. Ongoing research aims to identify these molecules.