Ancient Immune Mechanism Identified that Controls Malaria in Mosquitoes
NIAID’s Carolina Barillas-Mury, Ph.D., Chief, Mosquito Immunity and Vector Competence Unit, Laboratory of Malaria and Vector Research, Division of Intramural Research, and her team recently discovered that the mosquito uses the STAT pathway, an ancient immune mechanism shared among vertebrate animals, including humans, to control infection with the Plasmodium parasites that cause malaria.
When mosquitoes ingest human blood containing the sexual stages of the Plasmodium parasite, they become infected. Each parasite that escapes early recognition by the mosquito’s immune system advances to its oocyst stage and proliferates continuously during a two-week period, generating 5,000 to 10,000 new parasites.
Once a parasite transforms into an oocyst, it modifies its surface and forms a capsule. At this stage, the capsule was thought to provide cover for the parasite, enabling it to become “hidden” from the mosquito’s immune system—so scientists believed. Dr. Barillas-Mury and her team have found that this is not case. In fact, oocysts are under a prolonged attack from the mosquito’s immune system, regulated by the STAT pathway, which leads to the increased production of an enzyme called nitric oxide synthetase (NOS). NOS produces nitric oxide, a toxic compound also produced by the human immune system to control infections.
These findings have uncovered a natural immune mechanism that controls malaria parasite infection in the mosquito, and they reveal that the regulation of NOS by the STAT pathway is an ancient response. Killing mechanisms that target the oocyst stage are particularly attractive to scientists looking for ways to control disease transmission, as Plasmodium parasites require several days to complete this stage in their life cycle.
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