The Course of Plasmodium.yoelii Infection in Hereditary Persistence of Fetal Hemoglobin.

Abstract Malaria, caused by plasmodium species has great impact on human generations. Each year 300–500 million of people are diagnosed and 1 million die of the disease. Malaria probably become endemic about 10,000 years ago and it has affected human genome by strong selective pressure. Several human genetic diseases are thought to be the outcome of this pressure. Our current research is focused on understanding natural host defense mechanism of this disease, especially effect to human fetal hemoglobin expression to plasmodium species. Other investigator indicated growth of Plasmodium falciparum is retarded in the cell containing human fetal hemoglobin in vivo (Nature, 270:171), and transgenic mouse (transgenic of human fetal hemoglobin and knockout of mouse beta-major gene) infected with Plasmodium has longer survival compare to control.(Blood, 92:2520). Here we use transgenic mouse express human fetal hemoglobin (human Gamma globin) which simulate human hereditary persistence of fetal hemoglobin (PNAS86:7033) to investigate fetal hemoglobin itself has a protective effect on Plasmodium infection in vivo. We injected 1,000 Plasmodium.yoelii infected RBCs to transgenic mouse expressing human fetal hemoglobin (n=5) and C57BL6J mouse (n=8). Blood smears obtained daily and smears were stained with Giemsa. Parasitemia is calculated from about 1000 RBCs. 5 days after injection, infected RBCs was 26.4 ±4.7% for C57BL6J and 32.6± 17.3% for human fetal hemoglobin transgenic mouse. We couldn’t show significant difference between these groups. And 60% of C57BL6J mice (3 of 5) were recovered from illness. In contrast, 20% of transgenic mouse (1of 5) was recovered from illness. These results demonstrates only human fetal hemoglobin expression is not enough to contribute defense mechanism against plasmodium species.