Gut bacteriophages induce specific-reprogramming of macrophages to generate a protective innate immunity response to lipopolysaccharide exposure

文献类型： 外文期刊

第一作者： Hou, Xiang

作者： Hou, Xiang;Wang, Heye;Wang, Jing;Liu, Hui;Hu, Hao;Zhang, Lili;Hou, Xiang;Wang, Ran;Ding, Huiyan;Billington, Craig

作者机构：

关键词： Bacteriophage; innate immune memory; macrophage; IL-10; epigenetic mechanisms

期刊名称：GUT MICROBES （ 影响因子：11.0； 五年影响因子：13.4 ）

ISSN： 1949-0976

年卷期： 2025 年 17 卷 1 期

页码：

收录情况： SCI

摘要： Macrophages play essential roles in generating a tolerogenic resident environment, but the interactions between bacteriophages and their action in macrophage tolerance memory remain unknown. Here, we find that gut bacteriophage exposure in vivo induces tolerance immunity via reprogrammed macrophages which significantly enhances protection against bacterial lipopolysaccharide (LPS). Bacteriophage-memory macrophages orchestrate LPS-challenge responses into tolerization or hyperresponsive gene expression clusters in a function-specific manner. The tolerized gene cluster encodes pro-inflammatory cytokines, while the induction cluster is a defense-specific response including anti-inflammatory cytokines, antiviral and antimicrobial effectors, and negative regulators of inflammation. Mechanistically, this augmented defense response is dependent on increased expression of IL-10, but not suppression of pro-inflammatory cytokines. Furthermore, bacteriophages suppressed LPS-induced pro-inflammatory genes by repressing histone acetylation target enhancers that coordinate chromatin accessibility to limit inflammation. Thus, our study identifies the function and mechanism of reprogramming actions for bacteriophage in moderating LPS immune responses.

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