Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
Infect Immun. 2013 Oct;81(10):3865-71. doi: 10.1128/IAI.00749-13. Epub 2013 Jul 29.
Pregnant 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 during Plasmodium falciparum infection and investigated the pathogenesis of maternal malaria. Pregnant mice immunized by infection with an attenuated parasite, Plasmodium berghei XAT, were more susceptible to virulent P. berghei NK65 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 with P. berghei NK65 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 with P. berghei NK65 than in plasma from nonpregnant mice. These findings suggest that development of liver injury and placental pathology in pregnant immune mice challenged/infected with P. berghei NK65 is accompanied by enhanced production of proinflammatory cytokines.
孕妇由于免疫力低下，极易感染疟疾，除了自然流产、死胎、早产和低体重儿外，还增加了母亲患病或死亡的风险。然而，母体疟疾的详细发病机制尚不清楚。在这项研究中，我们评估了一种小鼠模型，该模型在感染恶性疟原虫时显示出与孕妇相似的严重病理特征，并研究了母体疟疾的发病机制。与未怀孕的小鼠相比，用减毒寄生虫（伯氏疟原虫 XAT）感染免疫的怀孕小鼠对毒力更强的伯氏疟原虫 NK65 的攻击/感染更为敏感，并且在怀孕后期表现出高水平的寄生虫血症和不良的妊娠结局，与胎盘病理有关，例如寄生红细胞的积累。值得注意的是，怀孕免疫的小鼠在感染伯氏疟原虫 NK65 后会发生与微泡脂肪浸润相关的肝损伤。这些病理特征类似于妊娠急性脂肪肝。与未怀孕的小鼠相比，感染伯氏疟原虫 NK65 的怀孕免疫小鼠的血浆中发现了更高水平的γ干扰素和一氧化氮（NO）。这些发现表明，在感染伯氏疟原虫 NK65 的怀孕免疫小鼠中，肝损伤和胎盘病理的发展伴随着促炎细胞因子的产生增加。
