Role of Type I and Type III Interferons in Pre-Erythrocytic Immunity to Malaria

About 220 million cases of malaria occur annually, resulting in nearly half a million deaths globally. U.S. military personnel are routinely exposed to malaria in several areas of active operations. Malaria control is hampered by the spread of drug resistance in the parasite (Plasmodium) and the lack of an effective vaccine. Even a moderately efficacious vaccine can provide efficient and cost-effective protection against disease to hundreds of thousands of people in resource-poor countries, as well as to tourists, international aid workers, and military personnel deployed to endemic countries. The liver is the first organ to be infected by Plasmodium. The parasite infects liver cells and grows within them, eventually giving rise to tens of thousands for more parasites that leave the liver and enter the blood stream – which is when the parasite causes most damage. A vaccine that targets the parasite while it is in the liver would prevent disease. The development of such a vaccine would be accelerated by a better understanding of the immune responses that occur during liver infection. Interferons are produced in response to a variety of infections, including when the liver is infected. They are either approved or are undergoing clinical trials for antiviral, anti-tumor and autoimmunity indications. However, they have rarely been examined in malaria. There is little knowledge of their impact on liver infection by Plasmodium. Our proposal will determine first, if different types of interferons prevent or increase Plasmodium's liver infection and second, if their activation or inhibition changes immune responses mounted by the host. This knowledge will be leveraged in the future to improve malaria vaccines that are under development.