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

Author:

Chen Liang1234,Shao Zhenxuan1234,Zhang Zengjie1234,Teng Wangsiyuan1234,Mou Haochen1234,Jin Xiaoqiang1234,Wei Shenyu5,Wang Zenan1234,Eloy Yinwang1234,Zhang Wenkan1234,Zhou Hao1234,Yao Minjun1234,Zhao Shenzhi1234,Chai Xupeng1234,Wang Fangqian1234,Xu Kaiwang1234,Xu Jianbin1234,Ye Zhaoming1234ORCID

Affiliation:

1. Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou City Zhejiang Province 310000 P. R. China

2. Orthopedics Research Institute of Zhejiang University Hangzhou City Zhejiang Province 310000 P. R. China

3. Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province Hangzhou City Zhejiang Province 310000 P. R. China

4. Clinical Research Center of Motor System Disease of Zhejiang Province Hangzhou City 310000 P. R. China

5. Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou City Zhejiang Province 310000 P. R. China

Abstract

AbstractDeep 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.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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