Yao Minjun, Chen Liang, Jin Xiaoqiang, Shao Zhenxuan, Xue Yucheng, Zhang Wenkan, Zhou Hao, Zhao Shenzhi, Mou Haochen, Chen Shixin, Yinwang Eloy, Zhang Jiahao, Wu Xiaoyong, Wang Kanbin, Zhou Chenhe, Cai Xunzi, Zhuang Chen, He Rongxin, Xu Jianbin, Ye Zhaoming
Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, Zhejiang, China.
Sci Adv. 2025 Aug 29;11(35):eadr1911. doi: 10.1126/sciadv.adr1911.
Bacteriophage therapy has been recognized as a promising anti-infection alternative, while its clinical therapeutic outcomes are compromised due to the development of bacterial resistance, ongoing host immune dysfunction at infection sites, and their failure to adequately revitalize host immunity. Here, we present a strategy for artificial antigen-directed immune labeling of bacteria, capitalizing on residual bacteriophage capsids on bacterial surfaces, which enable immune cells to achieve quicker bacterial recognition and clearance. Specifically, Mn@Man-phage anchored on bacterial surfaces and provided artificial recognition sites that enabled macrophages to phagocytize via mannose receptors, accompanied by enhanced bactericidal activity triggered by manganese ions in response to an infectious microenvironment. Moreover, immune labeling-activated macrophages enhanced antigen presentation at infection sites, further boosting specific T cell-mediated adaptive immune responses and infection eradication effects. Overall, this study illustrates a scalable bacteriophage immune therapy based on precise biological labeling and targeted modulation of immune responses, bridging the natural divide between bacteriophages and host immunity.
噬菌体疗法已被公认为一种有前景的抗感染替代方法，然而，由于细菌耐药性的产生、感染部位持续存在的宿主免疫功能障碍以及它们未能充分恢复宿主免疫力，其临床治疗效果受到影响。在此，我们提出一种针对细菌的人工抗原导向免疫标记策略，利用细菌表面残留的噬菌体衣壳，使免疫细胞能够更快地识别和清除细菌。具体而言，锚定在细菌表面的锰@甘露糖噬菌体提供了人工识别位点，使巨噬细胞能够通过甘露糖受体进行吞噬，同时，响应感染性微环境，锰离子触发增强的杀菌活性。此外，免疫标记激活的巨噬细胞增强了感染部位的抗原呈递，进一步促进了特异性T细胞介导的适应性免疫反应和感染根除效果。总体而言，本研究阐述了一种基于精确生物标记和靶向调节免疫反应的可扩展噬菌体免疫疗法，弥合了噬菌体与宿主免疫之间的天然鸿沟。
