Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 06, Oeiras 2780-156, Portugal.
Malar J. 2012 Jul 16;11:231. doi: 10.1186/1475-2875-11-231.
Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection.
A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared.
The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKAΔpm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites.
Infection of pregnant C57BL/6 females with K173, NK65 and ANKAΔpm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms.
胎盘疟疾(PM)是妊娠期间疟疾的一个主要特征。最近建立了一种使用感染疟原虫伯氏疟原虫 ANKA 的 BALB/c 小鼠的实验性 PM 小鼠模型,但需要具有不同寄生虫/宿主组合的其他 PM 模型,以研究特定宿主遗传因素在疟原虫感染引起的胎盘炎症反应中的作用。
采用中期感染方案,检测三种疟原虫系(源自疟原虫 K173、NK65 和 ANKA 株,但在易感 C57BL/6 小鼠中不能引起实验性脑疟疾 [ECM])感染对 PM 的诱导作用。比较三种寄生虫系引起的寄生虫血症过程、妊娠结局和胎盘病理学。
三种疟原虫系均能引起严重的 PM 病理和不良妊娠结局特征。结果表明,诱导 PM 所需的寄生虫成分与 ECM 不同。然而,与感染 NK65 和 K173 寄生虫相比,感染缺乏质膜蛋白酶 4 表达的 ANKAΔpm4 寄生虫的疾病表型较轻,与强烈的先天免疫反应相关。
用 K173、NK65 和 ANKAΔpm4 疟原虫感染怀孕的 C57BL/6 雌性小鼠提供了实验系统,可用于鉴定参与 PM 发病机制的宿主分子成分。