小柯机器人

葡萄牙古尔本基安科学研究所Miguel P. Soares团队发现一种对抗疟疾的低代谢防御策略。相关论文于2022年7月15日在线发表在《细胞—代谢》杂志上。

研究人员发现，与疟疾相关的低血糖症是由一种非经典的抵抗机制产生的，即受感染的宿主降低血糖来饿死疟原虫。这种低代谢反应是由游离亚铁血红素引起的，这是溶血的副产品，可诱发疾病引起的厌食，并抑制肝脏葡萄糖的产生。虽然对肝脏葡萄糖生产的短暂抑制可以防止不受约束的免疫介导的炎症、器官损伤和贫血，但如果长期持续，就会导致低血糖，损害宿主的能量消耗和适应性体温调节。

后者通过一种与寄生虫线粒体功能障碍有关的机制阻止疟原虫无性阶段的发展。作为回应，疟原虫激活了一个与降低毒力和性分化有关的转录程序，进而生成可传播的配子细胞。总之，疟疾相关的低血糖症代表了一种基于低代谢的防御策略的权衡，它平衡了寄生虫的毒力和传播。

据悉，低血糖症是严重疟疾的一个临床标志，是恶性疟原虫感染经常导致的致命结果。

附：英文原文

Title: A hypometabolic defense strategy against malaria

Author: Susana Ramos, Temitope W. Ademolue, Elisa Jentho, Qian Wu, Joel Guerra, Rui Martins, Gil Pires, Sebastian Weis, Ana Rita Carlos, Inês Mahú, Elsa Seixas, Denise Duarte, Fabienne Rajas, Sílvia Cardoso, António G.G. Sousa, Jingtao Lilue, Tiago Paixo, Gilles Mithieux, Fátima Nogueira, Miguel P. Soares

Issue&Volume: 2022-07-15

Abstract: Hypoglycemia is a clinical hallmark of severe malaria, the often-lethal outcome of Plasmodium falciparum infection. Here, we report that malaria-associated hypoglycemia emerges from a non-canonical resistance mechanism, whereby the infected host reduces glycemia to starve Plasmodium. This hypometabolic response is elicited by labile heme, a byproduct of hemolysis that induces illness-induced anorexia and represses hepatic glucose production. While transient repression of hepatic glucose production prevents unfettered immune-mediated inflammation, organ damage, and anemia, when sustained over time it leads to hypoglycemia, compromising host energy expenditure and adaptive thermoregulation. The latter arrests the development of asexual stages of Plasmodium via a mechanism associated with parasite mitochondrial dysfunction. In response, Plasmodium activates a transcriptional program associated with the reduction of virulence and sexual differentiation toward the generation of transmissible gametocytes. In conclusion, malaria-associated hypoglycemia represents a trade-off of a hypometabolic-based defense strategy that balances parasite virulence versus transmission.

DOI: 10.1016/j.cmet.2022.06.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00231-5

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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