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We have discovered that the mosquitoAnopheles stephensi , a natural vector of human malaria, limits parasite development with inducible synthesis of nitric oxide (NO). Elevated expression ofA. stephensi NO synthase (NOS), which is highly homologous to characterized NOS genes, was detected in the midgut and carcass soon after invasion of the midgut byPlasmodium . Early induction is likely primed by bacterial growth in the blood meal. Later increases inA. stephensi NOS expression and enzyme activity occurred at the beginning of sporozoite release. Circulating levels of nitrite/nitrate, end-products of NO synthesis, were significantly higher inPlasmodium -infected mosquitoes. Dietary provision of the NOS substratel -arginine reducedPlasmodium infections inA. stephensi . In contrast, dietary provision of a NOS inhibitor significantly increased parasite numbers in infected mosquitoes, confirming thatA. stephensi limitsPlasmodium development with NO.

The mosquitoAnopheles stephensilimits malaria parasite development with inducible synthesis of nitric oxide