title: Cell biological analysis of mosquito midgut invasion: the defensive role of the actin-based ookinete hood.
abstract: 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.
authors.forename: Timm
authors.initials: T
authors.lastname: Schlegelmilch
authors.forename: Dina
authors.initials: D
authors.lastname: Vlachou
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D009033:Culicidae / Q000276:immunology* / Q000469:parasitology*; D004847:Epithelial Cells / Q000276:immunology* / Q000469:parasitology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000469:parasitology; D054884:Host-Pathogen Interactions; D010961:Plasmodium / Q000254:growth & development*; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism
chemical_list: D000199:Actins; D051316:Wiskott-Aldrich Syndrome Protein
keywords: Anopheles gambiae,; Malaria,; Plasmodium,; host-parasite interactions; mosquito midgut invasion,; ookinete hood,