Mycobacterium tuberculosis manipulates LINC02528 in macrophages to modulate anti-tuberculosis metabolic immunity

Sep 29, 2026

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Host defenses shape the outcome of Mycobacterium tuberculosis (Mtb) infection, yet the pathways by which Mtb reshapes host redox balance to suppress immunity remain incompletely defined. This study identifies the pathogen-responsive long noncoding RNA LINC02528, selectively upregulated in peripheral blood mononuclear cells from tuberculosis patients. In Mtb-infected macrophages, LINC02528 relocalizes from nucleus to cytoplasm, and CRISPR-Cas9 knockout reduces bacterial survival while increasing IL-1β. Blocking IL-1 signaling with IL-RA eliminates these antimicrobial effects.

LanguageEnglish

CategoryHealthcare

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Pages25

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Abstract

Mechanism and key findings

OPEN ACCESS Citation: Xu Y, Zhang K, Li S, Qiao L, Mo S, Wang W, et al. (2025) Mycobacterium tuberculosis manipulates LINC02528 in macrophages to modulate anti-tuberculosis metabolic immunity. PLoS Pathog 21(12): e1013810. [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). ppat.1013810 Editor: Padmini Salgame, New Jersey Medical School, UNITED STATES OF AMERICA Received: June 15, 2025 Accepted: December 15, 2025 Published: December 23, 2025 Copyright: © 2025 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: All data are available in the manuscript and the Supporting Information files. Funding: This work was supported by the Shenzhen Medical Research Special Fund Project (A2304001, to XC); National Natural RESEARCH ARTICLE Mycobacterium tuberculosis manipulates LINC02528 in macrophages to modulate antituberculosis metabolic immunity Yuzhong Xu1,2,3☯, Kehong Zhang1,2☯, Sinan Li2, Lin Qiao2,4, Siwei Mo5, Wenfei Wang6, Jialou Zhu7, Xiaoqian Liu8, Ningjian Cai2,9, Chenyan Shi2, Yi Cai2, Yunlong Hu2*, Xinchun Chen2* 1 Department of Clinical Laboratory, Shenzhen Baoan Hospital/The Second Affiliated Hospital of Shenzhen University, Shenzhen University Medical School, Shenzhen, China, 2 Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, China, 3 Guangdong Provincial Clinical Research Center for Laboratory Medicine, Guangzhou, China, 4 College of biological sciences, China Agricultural University, Beijing, China, 5 Department of Laboratory Medicine, Affiliated Hospital of Zunyi Medical University/ Zunyi Medical University, Zunyi, China, 6 National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, China, 7 Department of Clinical Laboratory, Guangzhou Chest Hospital, Guangzhou/State Key Laboratory of Respiratory Disease, Guangzhou, China, 8 Department of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China, 9 National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China ☯ These authors contributed equally to this work. * [chenxinchun@szu.edu.cn](chenxinchun@szu.edu.cn) (XC); [huyunlong@szu.edu.cn](huyunlong@szu.edu.cn) (YH) Abstract Host defenses are crucial in deciding the fate of Mycobacterium tuberculosis (Mtb) infections, as less than 10% of infected individuals develop tuberculosis. Oxidative stress plays a critical role in the host defense against Mtb. However, the mechanisms by which Mtb modulates redox homeostasis to evade immune responses remain poorly understood. In this study, we primarily identified a pathogen-responsive long noncoding RNA, LINC02528, which was selectively upregulated in peripheral blood mononuclear cells (PBMCs) from tuberculosis (TB) patients. In Mtb-infected macrophages, LINC02528 dynamically relocalizes from the nucleus to the cytoplasm. Functionally, CRISPR-Cas9-mediated knockout (KO) of LINC02528 in macrophages resulted in reduced Mtb survival concurrent with an elevated IL-1β expression. Importantly, these antimicrobial effects were abrogated by IL-1 receptor antagonist (IL-RA) treatment. Interestingly, LINC02528 was found to directly bind to TOMM22, a mitochondrial outer membrane translocase, as validated by co-localization analysis using in situ hybridization of lung tissue sections from a TB patient. The ECAR results revealed that LINC02528 deficiency significantly increased glycolysis and elevated Mtb-indu

FAQs

What is LINC02528, and how is it linked to tuberculosis patients?

LINC02528 is a pathogen-responsive long noncoding RNA selectively upregulated in peripheral blood mononuclear cells from tuberculosis patients.

What happens when LINC02528 is knocked out in macrophages during Mtb infection?

CRISPR-Cas9 knockout of LINC02528 in macrophages reduces Mtb survival and increases IL-1β expression.

How do IL-1 pathway interventions affect the antimicrobial effects of LINC02528 loss?

Treatment with an IL-1 receptor antagonist (IL-RA) abrogates the antimicrobial effects caused by LINC02528 deficiency.

Sep 29, 2026

Uploaded by Kurz