Development of Severe Pathology in Immunized Pregnant Mice Challenged with Lethal Malaria Parasites

Abstract

ABSTRACTPregnant women are highly susceptible to malaria infection because of their low immunity and are at increased risk of maternal illness or death, in addition to spontaneous abortion, stillbirth, premature delivery, and low birth weight. However, the detailed pathogenesis of maternal malaria remains unclear. In this study, we evaluated a mouse model that shows similar severe pathological features of pregnant women duringPlasmodium falciparuminfection and investigated the pathogenesis of maternal malaria. Pregnant mice immunized by infection with an attenuated parasite,Plasmodium bergheiXAT, were more susceptible to virulentP. bergheiNK65 challenge/infection than were nonpregnant mice and showed high levels of parasitemia and a poor pregnancy outcome associated with placental pathology, such as accumulation of parasitized red blood cells, in the late phase of pregnancy. Notably, the pregnant immune mice challenged/infected withP. bergheiNK65 developed liver injury associated with microvesicular fatty infiltration in late pregnancy. The pathological features were similar to acute fatty liver of pregnancy. Higher levels of gamma interferon and nitric oxide (NO) were found in plasma from pregnant immune mice infected withP. bergheiNK65 than in plasma from nonpregnant mice. These findings suggest that development of liver injury and placental pathology in pregnant immune mice challenged/infected withP. bergheiNK65 is accompanied by enhanced production of proinflammatory cytokines.