Cell biological analysis of mosquito midgut invasion: the defensive role of the actin-based ookinete hood.

[wiskott-aldrich syndrome]

Successful completion of the Plasmodium lifecycle in the mosquito vector is critical for malaria transmission . It has been documented that the fate of Plasmodium in the mosquito ultimately depends on a fine interplay of molecular mosquito factors that act as parasite agonists and antagonists . Here we investigate whether the cellular responses of the invaded midgut epithelium can also determine the parasite fate and development . We show that the parasite hood , an actin-rich structure formed around the ookinete as it exits the epithelium , is a local epithelial defence reaction observed around 60 % of invading parasites . The hood co -localizes with WASP , a promoter of actin filament nucleation , suggesting that it is an active reaction of the invaded cell against invading parasites . Importantly , depletion of WASP by RNAi leads to a significant reduction in hood formation , which is consistent with the previously documented role of this gene as a potent parasite antagonist . Indeed , in mosquitoes that are either genetically selected or manipulated by RNAi to be refractory to Plasmodium , most dead parasites exhibit an actin hood . In these mosquitoes , invading ookinetes are killed by lysis or melanization while exiting the midgut epithelium . Silencing WASP in these mosquitoes inhibits the formation of the hood and allows many parasites to develop to oocysts . These data in conjunction with fine microscopic observations suggest that the presence of the hood is linked to ookinete killing through lysis .