Yang Fanfan, Liu Yuhui, Zhang Ying, Wei Dandan, Xie Zhongyi
Department of Microorganism Examination, Ningbo Center for Disease Control and Prevention, Ningbo, Zhejiang, China.
Department of Biochemistry and Molecular Biology, Jiangsu University, Jiangsu, Zhenjiang, China.
Virulence. 2025 Dec;16(1):2561828. doi: 10.1080/21505594.2025.2561828. Epub 2025 Sep 19.
serovar Typhi (. Typhi) is a major bacteria responsible for foodborne illnesses. Understanding the temporal dynamics of the host immune response and associated metabolic reprogramming is crucial for identifying potential therapeutic targets. This study employed an integrated transcriptomic and metabolomic approach to investigate the response of macrophages infected with . Typhi over a defined stage (0 h, 2 h, 4 h, 8 h, and 24 h). RNA sequencing (RNA-seq) was used to profile gene expression changes, while untargeted metabolomics characterized metabolic shifts. Gene set enrichment and pathway analyses were conducted to identify key immune and metabolic pathways. Additionally, Convergent Cross-Mapping (CCM) analysis was applied to uncover causal relationships between gene expression and metabolite fluctuations. Transcriptomic revealed distinct temporal phases of immune activation. Early responses were dominated by interferon signaling, cytokine production, and inflammatory responses, whereas later stages involved sustained immune signaling and metabolic adaptation. Key pathways, including NF-κB, TNF, and cytokine-cytokine receptor interactions, were significantly enriched. Metabolomic profiling demonstrated a transition from glycolysis and amino acid metabolism in early infection stages to fatty acid oxidation and mitochondrial function in later stages, with glutathione metabolism playing a central role in oxidative stress regulation. CCM analysis identified critical genes (e.g. RGS4, KIF18A, RSPO1) exhibiting strong causal relationships with metabolic alterations, underscoring the tight integration between immune and metabolic responses. This study provides a comprehensive, time-resolved view of . Typhi infection, highlighting dynamic immune activation and metabolic reprogramming in macrophages. These findings advance our understanding of host-pathogen interactions.
伤寒血清型（伤寒杆菌）是导致食源性疾病的主要细菌。了解宿主免疫反应的时间动态以及相关的代谢重编程对于确定潜在的治疗靶点至关重要。本研究采用综合转录组学和代谢组学方法，研究伤寒杆菌感染的巨噬细胞在特定阶段（0小时、2小时、4小时、8小时和24小时）的反应。RNA测序（RNA-seq）用于分析基因表达变化，而无靶向代谢组学则对代谢变化进行表征。进行基因集富集和通路分析以确定关键的免疫和代谢通路。此外，应用收敛交叉映射（CCM）分析来揭示基因表达与代谢物波动之间的因果关系。转录组学揭示了免疫激活的不同时间阶段。早期反应以干扰素信号传导、细胞因子产生和炎症反应为主，而后期则涉及持续的免疫信号传导和代谢适应。包括NF-κB、TNF和细胞因子-细胞因子受体相互作用在内的关键通路显著富集。代谢组学分析表明，在感染早期从糖酵解和氨基酸代谢转变为后期的脂肪酸氧化和线粒体功能，谷胱甘肽代谢在氧化应激调节中起核心作用。CCM分析确定了与代谢改变具有强因果关系的关键基因（如RGS4、KIF18A、RSPO1），强调了免疫和代谢反应之间的紧密整合。本研究提供了伤寒杆菌感染的全面、时间分辨视图，突出了巨噬细胞中动态免疫激活和代谢重编程。这些发现推进了我们对宿主-病原体相互作用的理解。
