ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicDeciphering Host-Pathogen Interactions in Tuberculosis: Implications for Diagnostics and TherapeuticsView all 14 articles
Elevated miR-17-5p Facilitates Mycobacterial Immune Evasion by Targeting MAP3K2 in Macrophages
Provisionally accepted
- 1School of Life Science, Central South University, Changsha, China
- 2Hunan Normal University, Changsha, China
- 3Hunan Chest Hospital, Changsha, China, Chang, China
- 4Third Xiangya Hospital of Central South University, Changsha, China
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Tuberculosis (TB) continues to be a significant global health challenge, affecting millions worldwide. Mycobacterium avium (M. avium), a non-tuberculosis mycobacterium, causes pulmonary infections and can evade immune surveillance, persisting within macrophages. MicroRNAs (miRNAs) are emerging as important regulators of host immune responses; however, their specific roles during mycobacterial pathogenesis remain largely unexplored. The objective of this study was to elucidate the effect of miR-17-5p in macrophage-mediated immune responses upon M. avium infection and it's impact on MAPK signaling through MAP3K2 regulation. We identified differentially expressed miRNAs using small RNA (sRNA) sequencing of exosomes from M. avium-infected THP-1 macrophages. Candidate miRNAs were confirmed by RT-qPCR in THP-1-infected exosomes and serum from TB patients. MAP3K2 was characterized as a miR-17-5p-regulated target via bioinformatics, luciferase assay, and expression analysis. Functional effects on immune responses and MAPK signaling were assessed via qPCR, ELISA, Western blotting, ROS measurement, and CFU assays. miR-17-5p was notably elevated in M. avium-infected macrophages, as well as in serum and peripheral blood monocytic cells (PBMCs) from TB patients. This overexpression suppressed MAP3K2 expression and attenuated MAPK signaling by reducing ERK, JNK, and p38 phosphorylation. This led to reduced production of inflammatory mediators (TNF-α, IL-6, and IL-1β), decreased iNOS and ROS levels, and ultimately impaired bacterial clearance. Overall, miR-17-5p promotes M. avium survival by targeting MAP3K2 and suppressing MAPK-dependent immune functions in macrophages. These findings identify miR-17-5p as a possible diagnostic marker and therapeutic target in TB and related mycobacterial infections.
Keywords: Mycobacterium tuberculosis, M. Avium, miR-17-5p, MAP3K2, Inflammation, Diagnostic marker
Received: 30 Jul 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Tang, JAHAN, Yang, Tang, Xiong, Hu and Tang. 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: Li Jun Tang, tljxie@csu.edu.cn
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