Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal presentation of Plasmodium falciparum infection of humans. Here we report that mice reduce blood glucose levels in response to Plasmodium infection via a coordinated response whereby labile heme, an alarmin produced via hemolysis, induces anorexia and represses hepatic glucose production (HGP). While protective against unfettered immune-mediated inflammation, organ damage and anemia, when sustained over time heme-driven repression of HGP can progress towards hypoglycemia, compromising host energy expenditure and thermoregulation. This hypometabolic state arrests the development of asexual stages of Plasmodium spp., which undergo pyknosis and develop mitochondrial dysfunction. In response, Plasmodium activates a transcriptional program reducing its virulence and inducing sexual differentiation towards the production of transmissible gametocytes. We infer that malaria-associated hypoglycemia represents a trade-off of an evolutionarily conserved defense strategy restricting Plasmodium spp. from accessing host-derived glucose and balancing parasite virulence and transmission.

中文翻译：

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抗疟原虫感染的低代谢防御策略

低血糖是严重疟疾的临床标志，这是人类恶性疟原虫感染的常见致死表现。在这里我们报告小鼠通过协调反应降低血糖水平以响应疟原虫感染，其中不稳定的血红素（一种通过溶血产生的警报）诱导厌食并抑制肝葡萄糖产生（HGP）。虽然对不受限制的免疫介导的炎症、器官损伤和贫血有保护作用，但随着时间的推移，血红素驱动的 HGP 抑制会发展为低血糖，从而损害宿主能量消耗和体温调节。这种低代谢状态阻止了疟原虫无性阶段的发展., 发生固缩并发展为线粒体功能障碍。作为回应，疟原虫激活转录程序，降低其毒力并诱导产生可传播配子体的性分化。我们推断，疟疾相关的低血糖症代表了限制疟原虫属的进化保守防御策略的权衡。从获取宿主来源的葡萄糖和平衡寄生虫毒力和传播。