An On‐Demand Collaborative Innate–Adaptive Immune Response to Infection Treatment

• Published in: Advanced materials (Weinheim) 2024-04, Vol.36 (15), p.e2304774-n/a
• Main Authors: Chen, Liang, Shao, Zhenxuan, Zhang, Zengjie, Teng, Wangsiyuan, Mou, Haochen, Jin, Xiaoqiang, Wei, Shenyu, Wang, Zenan, Eloy, Yinwang, Zhang, Wenkan, Zhou, Hao, Yao, Minjun, Zhao, Shenzhi, Chai, Xupeng, Wang, Fangqian, Xu, Kaiwang, Xu, Jianbin, Ye, Zhaoming
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Anti-Bacterial Agents - metabolism; antibacterial immunotherapies; Antiinfectives and antibacterials; artificially reprogrammed cells; Bacteria; bacterial infections; Biomimetics; Collaboration; Humans; immune recovery; Immune system; Immunity, Innate; Infections; Lymphocytes; Macrophages; Macrophages - metabolism; Mannose; Recurrence
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202304774

Deep tissue infection is a common clinical issue and therapeutic difficulty caused by the disruption of the host antibacterial immune function, resulting in treatment failure and infection relapse. Intracellular pathogens are refractory to elimination and can manipulate host cell biology even after appropriate treatment, resulting in a locoregional immunosuppressive state that leads to an inadequate response to conventional anti‐infective therapies. Here, a novel antibacterial strategy involving autogenous immunity using a biomimetic nanoparticle (NP)‐based regulating system is reported to induce in situ collaborative innate–adaptive immune responses. It is observed that a macrophage membrane coating facilitates NP enrichment at the infection site, followed by active NP accumulation in macrophages in a mannose‐dependent manner. These NP‐armed macrophages exhibit considerably improved innate capabilities, including more efficient intracellular ROS generation and pro‐inflammatory factor secretion, M1 phenotype promotion, and effective eradication of invasive bacteria. Furthermore, the reprogrammed macrophages direct T cell activation at infectious sites, resulting in a robust adaptive antimicrobial immune response to ultimately achieve bacterial clearance and prevent infection relapse. Overall, these results provide a conceptual framework for a novel macrophage‐based strategy for infection treatment via the regulation of autogenous immunity. Macrophages play crucial roles in bridging both host innate and adaptive anti‐infectious immunity while their intrinsic bactericidal function is compromised with prolonged infection progressing. After in situ nanoparticle arming, macrophages in infection sites demonstrate substantially augmented antimicrobial activities and also facilitate the reversal of the immunosuppressive microenvironment, which thus realizes infection control and recurrence prevention in an on‐demand manner.