感染和败血症中的生理紊乱和新陈代谢重编程。

Cell metabolism Pub Date : 2024-05-07 Epub Date: 2024-03-20 DOI:10.1016/j.cmet.2024.02.013
Katharina Willmann, Luis F Moita
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引用次数: 0

摘要

要有效应对严重的全身性感染,就必须协调两种互补的防御策略,最大限度地减少感染对宿主的负面影响:一种是旨在消灭病原体的抵抗力,另一种是限制组织损伤和保护器官功能的疾病耐受力。抵抗力和疾病耐受力主要依赖于不同的新陈代谢程序,这些程序在时间和空间上可能不会同时运行。由于进化的原因,宿主最初会优先考虑消灭病原体,从而形成占主导地位的抵抗机制,但可能会牺牲疾病耐受性,导致器官功能衰竭。在此,我们总结了我们目前对感染导致的生理扰动在免疫反应动态中的作用以及与抗性和疾病耐受机制相关的代谢程序要求的理解。然后,我们将讨论如何深入了解这些机制的相互作用,为今后旨在改善败血症预后的研究提供信息,并探讨治疗干预措施的潜力。
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Physiologic disruption and metabolic reprogramming in infection and sepsis.

Effective responses against severe systemic infection require coordination between two complementary defense strategies that minimize the negative impact of infection on the host: resistance, aimed at pathogen elimination, and disease tolerance, which limits tissue damage and preserves organ function. Resistance and disease tolerance mostly rely on divergent metabolic programs that may not operate simultaneously in time and space. Due to evolutionary reasons, the host initially prioritizes the elimination of the pathogen, leading to dominant resistance mechanisms at the potential expense of disease tolerance, which can contribute to organ failure. Here, we summarize our current understanding of the role of physiological perturbations resulting from infection in immune response dynamics and the metabolic program requirements associated with resistance and disease tolerance mechanisms. We then discuss how insight into the interplay of these mechanisms could inform future research aimed at improving sepsis outcomes and the potential for therapeutic interventions.

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