Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Innate Immunity and Inflammation Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal; Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Cell Metab. 2024 May 7;36(5):927-946. doi: 10.1016/j.cmet.2024.02.013. Epub 2024 Mar 20.
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.
有效应对严重全身感染需要协调两种互补的防御策略，以最大限度地减少感染对宿主的负面影响：抵抗，旨在消除病原体；和疾病耐受，限制组织损伤并维持器官功能。抵抗和疾病耐受主要依赖于不同的代谢程序，这些程序可能不会在时间和空间上同时运行。由于进化原因，宿主最初优先消除病原体，导致抵抗机制占主导地位，可能以牺牲疾病耐受为代价，这可能导致器官衰竭。在这里，我们总结了我们目前对感染引起的生理干扰在免疫反应动力学中的作用以及与抵抗和疾病耐受机制相关的代谢程序要求的理解。然后，我们讨论了深入了解这些机制的相互作用如何为旨在改善败血症结果和治疗干预潜力的未来研究提供信息。
