ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1606401
This article is part of the Research TopicMolecular mechanisms and clinical studies of multi-organ dysfunction in sepsis associated with pathogenic microbial infectionView all 19 articles
LILRA5 + Macrophages Drive Early Oxidative Stress Surge in Sepsis: A Single-Cell Transcriptomic Landscape with Therapeutic Implications
Provisionally accepted
- 1Department of General Surgery, Northern Theater Command, Shenyang, China
- 2Beijing Haidian Hospital, Peking University, Haidian, Beijing, China
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Background: In sepsis, oxidative stress (OS) triggers essential adaptive responses and emerging oxidative stress-related biomarkers show potential for enhancing sepsis diagnosis and therapy. Methodology: In this study, we used single-cell datasets and the OS gene set to identify immune cell types with the highest oxidative activity across different sepsis states. Differential expression genes (DEG) between "high state" cells and "low state" cells were screened out. hdWGCNA analysis, combining with multiple machine learning methods, was used for hub genes sellection. Expressions of hub genes were then validated. Cell-cell communication and transcription factors analysis were performed later. qRT-PCR and Western blotting validated expression of LILRA5 in both the cecal ligation and puncture (CLP) model and Lipopolysaccharide-induced sepsis model. Reactive oxygen species (ROS) levels were also detected in THP-1 cells after silencing LILRA5. Results: In the early stages of sepsis, oxidative activity reaches its peak, with macrophages displaying the highest oxidative stress among all cell types.Through the application of the "Quartile method", all cells were clustered into three state based on OS activity (low, median, high). LILRA5, MGST1, PLBD1, and S100A9 were sellected as hub genes and significantly up-regulated in sepsis. LILRA5 was predominantly expressed in macrophages and LILRA5 highly expressed in the early stage of macrophage. Specifically, LILRA5+ macrophages exhibit the strongest oxidative stress. LILRA5 showed a higher expression in both mice sepsis models and the THP-1 cell after lipopolysaccharide stimulating. Silencing LILRA5 was results in a significant reduction of reactive oxygen species (ROS) in THP-1 cells. Conclusion: In conclusion, our study has mapped the landscape of oxidative stress dynamics in sepsis and found that LILRA5+ macrophages in the early stage of sepsis exhibit the highest OS. LILRA5 emerges as a promising gene for modulating macrophage-mediated OS in sepsis.
Keywords: Oxidative Stress, Sepsis, LILRA5, macrophage, single-cell
Received: 05 Apr 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Xu, Li, Tao, Zhang, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Cheng Zhang, Department of General Surgery, Northern Theater Command, Shenyang, China
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