FIGURE 8.

Schematic diagram showing the possible role of AGAP001476 in anti-Plasmodium response via TEP1-mediated lysis. When Plasmodium is ingested through an infective blood meal, Plasmodium gametocytes undergo sexual reproduction and develop into ookinetes in the mosquito midgut. The ingestion of blood meal and Plasmodium traversal through the midgut epithelial cell induced the Toll pathway of innate immune responses, partly via a yet to be known signal through the innexon hemichannel. The expression of innexin AGAP001476 in midgut increases upon infection. It is uncertain how innexons containing AGAP001476 transduce signal from midgut to hemocytes and fat body. The induction of Toll pathway induces the expression of complement-like protein TEP1 and nutrient transport protein Vg, which inhibits TEP1 function. TEP1 then targets ookinetes that become exposed to the hemolymph in the basal lamina for killing. When innexons are blocked by carbenoxolone or innexin AGAP001476 is reduced by gene silencing, the induction of Toll pathway would become hampered. This leads to a reduced level of TEP1 released from hemocytes and thus formation of functional TEP1-LRIM1-APL1C complex. The elevated level of Vg from fat body cells in turn inhibits the action of the already reduced TEP1. The lowered bioavailability of functional TEP1 thus results in an increase of ookinete survival and oocyst number.