Xu Wei, Wu Yuan, Yang Min, Zhou Jiayu, Zhu Liying, Ma Xiaosai, Qiu Chonghai, Shen Ling, Shen Hongbo, Wang Feifei
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Department of Medical Microbiology and Parasitology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Microbiology & Immunology and Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, IL, United States.
Front Immunol. 2025 Jul 4;16:1567167. doi: 10.3389/fimmu.2025.1567167. eCollection 2025.
Exosomes, known as small membrane vesicles of endocytic origin produced by most cell types, exist in a variety of body fluids including plasma. The roles of exosomes in immune responses against () infection remain poorly characterized. Here, we found that miR-107 highly expressed in exosomes from plasma of TB patients but not healthy control (HC) subjects. Consistently, such miR-107-high exosomes were also detected in both the extracellular fluid released by mycobacterial-infected macrophages and the plasma of mycobacterial-infected mice. Interestingly, adding the miR-107-high plasma exosomes or the miR-107 mimics to infected THP-1 macrophages inhibited intracellular mycobacterial growth. Consistently, while nanoscale and fluorescence imaging revealed that miR-107 could be transferred inter-cellularly via exosomes, miR-107-enriched exosomes from miR-107 overexpressing cells also inhibited mycobacterial growth in THP-1 macrophages and primary monocytes/peripheral blood mononuclear cells (PBMC). Mechanistically, miR-107-high exosomes increased ROS production; miR-107 regulated Wnt pathway by targeting Wnt16 and promoted autophagy in THP-1 macrophages. Furthermore, treatment of infected mice with miR-107-enriched exosomes reduced mycobacterial infection in lung tissues. Our results raise a possibility to explore miR-107-high plasma exosomes for a potential surrogate marker for TB. Findings suggest that exosomes enriched with miR-107 or other bio-active molecules may potentially serve as an attractive approach for treatment of infection.
外泌体是大多数细胞类型产生的内吞来源的小膜泡，存在于包括血浆在内的多种体液中。外泌体在针对（）感染的免疫反应中的作用仍未得到充分表征。在这里，我们发现miR-107在结核病患者血浆而非健康对照（HC）受试者的血浆外泌体中高度表达。同样，在分枝杆菌感染的巨噬细胞释放的细胞外液和分枝杆菌感染的小鼠血浆中也检测到了这种miR-107高表达的外泌体。有趣的是，将miR-107高表达的血浆外泌体或miR-107模拟物添加到感染的THP-1巨噬细胞中可抑制细胞内分枝杆菌的生长。同样，虽然纳米级和荧光成像显示miR-107可以通过外泌体在细胞间转移，但来自miR-107过表达细胞的富含miR-107的外泌体也抑制了THP-1巨噬细胞和原代单核细胞/外周血单核细胞（PBMC）中的分枝杆菌生长。从机制上讲，miR-107高表达的外泌体增加了ROS的产生；miR-107通过靶向Wnt16调节Wnt通路并促进THP-1巨噬细胞中的自噬。此外，用富含miR-107的外泌体治疗感染的小鼠可减少肺组织中的分枝杆菌感染。我们的结果提出了探索miR-107高表达的血浆外泌体作为结核病潜在替代标志物的可能性。研究结果表明，富含miR-107或其他生物活性分子的外泌体可能是治疗感染的一种有吸引力的方法。
