Alpha-tocopherol transfer protein gene inhibition enhances the acquired immune response during malaria infection in mice

Immune response to malaria infection is complex and seems to be regulated by innate and adaptive immune response as well as environmental factors such as host genetics and nutritional status. Previously, we have reported that alpha-tocopherol transfer protein knockout (alpha-ttp(Delta)) mice, showing low concentrations of a-tocopherol in circulation, infected with Plasmodium berghei NK65 survived significantly longer as compared with the wild-type mice. In addition, Plasmodium yoelii XL-17, a lethal strain, showed non-lethal virulence in alpha-ttp(Delta) mice. Thus, we hypothesized that the ability of the alpha-ttp(Delta) mice to control P. yoelli XL-17 proliferation may allow them to build an efficient immune response against murine malaria infection. On 15 days after infection with P. yoelli XL-17, alpha-ttp(Delta) mice were challenged to infection with P. berghei NK65. Results indicated that alpha-ttp(Delta) mice infected with P. yoelli XL-17 built a protective immunity against P. berghei NK65 associated to extremely low levels of parasitemia, a controlled inflammatory response, and a robust antibody response. Moreover, the importance of alpha-tocopherol for parasite proliferation was remarkable. The results suggest that inhibition of alpha-tocopherol transfer protein activity is effective for the enhancement of acquired immunity in murine malaria infection.