Protection from lethal malaria in transgenic mice expressing sickle hemoglobin

Abstract

Previous studies from our laboratories have shown that transgenic mice expressing high levels of β(s) globin are well-protected from Plasmodium chabaudi adami and partially protected against P berghei (Shear et el, Blood 81:222, 1993). We have now infected transgenic mice expressing low (39%), intermediate (57%), and high (75%) levels of β(s) with the virulent strain of P yoelii (17XL) that appears to cause cerebral malaria. We find that the level of protection in these three groups of mice correlates positively with the level of β(s) chain expression in the mice. Seven of nine mice expressing the high level of β(s) recovered from infection, as did 7 of 9 mice expressing the intermediate level of β(s). Control mice and mice expressing the lower level of β(s) all succumbed to infection. In mice expressing high and intermediate levels of β(s) parasites were found almost exclusively in reticulocytes during recovery, suggesting that mature red blood cells expressing β(s) are more resistant than reticulocytes. These studies confirm epidemiologic data and offer insight into the mechanism of protection of sickle trait individuals against falciparum malaria.