The relevance of genetic factors in conferring protection to severe malaria has been demonstrated, as in the case of sickle cell trait and G6PD deficiency ¹ . However, it remains unknown whether environmental components, such as dietary or metabolic variations, can contribute to the outcome of infection ² . Here, we show that administration of a high-fat diet to mice for a period as short as 4 days impairs Plasmodium liver infection by over 90%. Plasmodium sporozoites can successfully invade and initiate replication but die inside hepatocytes, thereby are unable to cause severe disease. Transcriptional analyses combined with genetic and chemical approaches reveal that this impairment of infection is mediated by oxidative stress. We show that reactive oxygen species, probably spawned from fatty acid β-oxidation, directly impact Plasmodium survival inside hepatocytes, and parasite load can be rescued by exogenous administration of the antioxidant N-acetylcysteine or the β-oxidation inhibitor etomoxir. Together, these data reveal that acute and transient dietary alterations markedly impact the establishment of a Plasmodium infection and disease outcome.

中文翻译：

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饮食改变会改变对疟原虫感染的敏感性。

与镰状细胞性状和G6PD缺乏症¹一样，已经证明了遗传因素在赋予对严重疟疾的保护中具有相关性。但是，尚不清楚环境因素（例如饮食或代谢变化）是否会导致感染的结果²。在这里，我们显示高脂饮食对小鼠的短至4天的给药时间会损害超过90％的疟原虫肝感染。疟原虫子孢子可成功侵入并开始复制，但在肝细胞内死亡，因此不能引起严重的疾病。转录分析与遗传和化学方法相结合表明，这种感染的损害是由氧化应激介导的。我们显示，可能由脂肪酸β-氧化产生的活性氧直接影响肝细胞内的疟原虫存活，并且通过外源性给予抗氧化剂N-乙酰半胱氨酸或β-氧化抑制剂依托莫昔可以挽救寄生虫的负荷。一起，