Plasmodium signaling of innate immunity in Anopheles

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DESCRIPTION (provided by the applicant): The Anopheles stephensi nitric oxide synthase (AsNOS)-mediated defense was the first described from a vector mosquito that is both naturally induced by and inhibitory to parasite development. This defense is shared by mosquito and human hosts of Plasmodium. In preliminary experiments, AsNOS expression in immortalized A. stephensi cells was induced by a purified signaling factor from Plasmodium falciparum. Studies previous to ours demonstrated that this parasite factor is sufficient to induce the synthesis of inflammatory cytokines and NO by mammalian cells. By extension from work with mammalian cells, we propose to determine whether this parasite factor is necessary and sufficient to mimic parasite activation of AsNOS and to determine whether pathways involved in parasite signaling of AsNOS induction are conserved with those involved in parasite signaling of iNOS induction in mammalian cells. Ultimately, signaling pathways that relay specific information of parasite infection could be targeted directly to modify expression of AsNOS or used as tools to identify novel downstream anti-parasite effectors that could be targeted for the development of Plasmodium-resistant Anopheles.