Divergent metabolic rewiring shapes altered innate immunity

IF 2.9 4区医学 Q2 CELL BIOLOGY

Cellular immunology Pub Date : 2025-09-06 DOI:10.1016/j.cellimm.2025.105025

Mohua Liu, Xiao Wang, Xiaoya Qu, Yao Wang, Xihui Shen, Lei Xu

引用次数: 0

Abstract

Both trained immunity (TRIM) and endotoxin tolerance (ET) initiate similar metabolic reprogramming characterized by enhanced glycolysis following an initial stimulus. However, TRIM exhibited heightened immune activation upon restimulation, whereas ET showed suppressed innate immune response. This divergence is attributed to distinct metabolic intermediates accumulated after the initial stimulation. In TRIM, metabolites like fumarate and glutamine derivatives accumulate, reinforcing pro-inflammatory epigenetic modifications. Conversely, ET is characterized by increased itaconate and lactate levels, promoting anti-inflammatory epigenetic changes and metabolic paralysis. This review highlights metabolic intermediates as key regulators of innate immune fate decisions, presenting avenues for targeted immune modulation.

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不同的代谢重塑改变了先天免疫

训练免疫（TRIM）和内毒素耐受性（ET）启动类似的代谢重编程，其特征是初始刺激后糖酵解增强。然而，TRIM在再刺激后表现出增强的免疫激活，而ET表现出抑制的先天免疫反应。这种差异归因于初始刺激后积累的不同代谢中间体。在TRIM中，富马酸盐和谷氨酰胺衍生物等代谢物积累，加强了促炎症的表观遗传修饰。相反，ET的特点是衣康酸和乳酸水平升高，促进抗炎表观遗传改变和代谢瘫痪。这篇综述强调了代谢中间体作为先天免疫命运决定的关键调节因子，提出了靶向免疫调节的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cellular immunology 生物-免疫学

CiteScore

8.20

自引率

2.30%

发文量

102

审稿时长

30 days

期刊介绍： Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.