Hirako Isabella Cristina, Ramalho Theresa, Gazzinelli Ricardo Tostes
Laboratory of Immunopathology - Instituto René Rachou, Fundação Oswaldo Cruz - Minas, Belo Horizonte 30190-002, Brazil.
Department of Molecular Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Philos Trans R Soc Lond B Biol Sci. 2025 Jan 23;380(1918):20230511. doi: 10.1098/rstb.2023.0511.
The synchronization of parasites as they replicate within red blood cells of their vertebrate host remains largely unexplored. Understanding this synchronization could reveal how parasites optimize their lifecycle to maximize transmission, evade the immune response and maximize energy acquisition. Rhythmic replication fulfils some criteria of an endogenous oscillator with time of day cues potentially provided by temperature, oxygen levels, hormones and/or nutrient availability. Recent research on a rodent malaria model has highlighted that rhythms associated with the host's feeding/fasting cycle are a crucial factor influencing the synchronization of the erythrocytic stages of to the host's circadian cycle. Innate immune responses are also rhythmic and can regulate host metabolism, suggesting that the innate immune response triggered by contributes to its rhythmic replication. Here, we outline how the interplay between immune responses and metabolism could influence the timing and synchronization of 's replication rhythm, focusing on the roles of the cytokine tumour necrosis factor, mitochondrial function and metabolites generated by the tricarboxylic acid cycle in highly activated monocytes. These processes are pivotal in controlling parasitemia and determining disease outcome, suggesting that a better understanding of energy metabolism on rhythmic host-parasite interactions may provide new insights for therapeutic interventions against malaria.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.
寄生虫在脊椎动物宿主的红细胞内复制时的同步化现象在很大程度上仍未得到充分探索。了解这种同步化现象可以揭示寄生虫如何优化其生命周期，以实现传播最大化、逃避免疫反应并最大限度地获取能量。有节奏的复制符合内源性振荡器的一些标准，一天中的时间线索可能由温度、氧气水平、激素和/或营养物质的可用性提供。最近对啮齿动物疟疾模型的研究强调，与宿主进食/禁食周期相关的节律是影响疟原虫红细胞阶段与宿主昼夜节律同步的关键因素。先天免疫反应也是有节奏的，并且可以调节宿主代谢，这表明由疟原虫触发的先天免疫反应有助于其有节奏的复制。在这里，我们概述了免疫反应和代谢之间的相互作用如何影响疟原虫复制节律的时间和同步化，重点关注细胞因子肿瘤坏死因子、线粒体功能以及三羧酸循环在高度活化的单核细胞中产生的代谢产物的作用。这些过程在控制寄生虫血症和确定疾病结果方面至关重要，这表明更好地理解能量代谢对宿主-寄生虫节律性相互作用的影响可能为疟疾治疗干预提供新的见解。本文是西奥·墨菲会议议题“感染与免疫中的昼夜节律”的一部分。
