Host-mediated regulation of superinfection in malaria.
Host-mediated regulation of superinfection in malaria.
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作者：
在疟疾传播高发的地区，蚊子反复将嗜肝疟原虫子孢子传播给已经患有血液期寄生虫血症的个体。这在年龄较大的半免疫儿童中通过在低无症状寄生虫血症中同时携带不同的寄生虫基因型而表现出来。在免疫力较低的个体中，双重感染会增加高寄生虫血症和死亡的风险，但与直觉相反的是，在年轻人中并不常见。在这里，我们在啮齿动物模型中显示，持续的血液阶段感染，高于最低阈值，会损害随后接种的子孢子的生长，使得它们在肝细胞中生长停滞，并且无法发育成血液阶段寄生虫。肝脏阶段的抑制可以通过宿主铁调节激素铁调素介导，血液阶段寄生虫以密度依赖性方式刺激铁调素的合成。我们对这种现象进行了建模，并展示了针对肝期疟疾的密度依赖性保护如何塑造幼儿中疟疾感染的年龄相关风险和复杂性的流行病学模式。这两个疟原虫阶段与宿主铁代谢之间的相互作用与全球减少疟疾传播的努力以及疟疾流行地区补充铁的营养计划具有相关性。
In regions of high malaria transmission, mosquitoes repeatedly transmit liver-tropic Plasmodium sporozoites into individuals who already have blood-stage parasitaemia. This manifests itself in older semi-immune children by concurrent carriage of different parasite genotypes at low asymptomatic parasitaemias. Superinfection presents an increased risk of hyperparasitaemia and death in less immune individuals, but counter-intuitively is not frequently observed in the young. Here, we show in a rodent model, that ongoing blood-stage infections, above a minimum threshold, impair the growth of subsequently inoculated sporozoites such that they become growth arrested in liver hepatocytes and fail to develop into blood-stage parasites. Inhibition of the liver-stage can be mediated by the host iron regulatory hormone hepcidin, the synthesis of which is stimulated by blood-stage parasites in a density-dependent manner. We model this phenomenon and show how density-dependent protection against liver-stage malaria can shape the epidemiological patterns of age-related risk and complexity of malaria infections seen in young children. The interaction between these two Plasmodium stages and host iron metabolism has relevance for the global efforts to reduce malaria transmission and for nutritional programmes of iron supplementation in malaria-endemic regions.
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