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Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways

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  • Chuang Yang

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University)

  • Yao Luo

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University)

  • Hao Shen

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University)

  • Min Ge

    (Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences)

  • Jin Tang

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Qiaojie Wang

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University)

  • Han Lin

    (Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences)

  • Jianlin Shi

    (Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences)

  • Xianlong Zhang

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Jiao Tong University)

Abstract

Strategies to manipulate immune cell co-inhibitory or co-activating signals have revolutionized immunotherapy. However, certain immunologically cold diseases, such as bacterial biofilm infections of medical implants are hard to target due to the complexity of the immune co-stimulatory pathways involved. Here we show that two-dimensional manganese chalcogenophosphates MnPSe3 (MPS) nanosheets modified with polyvinylpyrrolidone (PVP) are capable of triggering a strong anti-bacterial biofilm humoral immunity in a mouse model of surgical implant infection via modulating antigen presentation and costimulatory molecule expression in the infectious microenvironment (IME). Mechanistically, the PVP-modified MPS (MPS-PVP) damages the structure of the biofilm which results in antigen exposure by generating reactive oxidative species, while changing the balance of immune-inhibitory (IL4I1 and CD206) and co-activator signals (CD40, CD80 and CD69). This leads to amplified APC priming and antigen presentation, resulting in biofilm-specific humoral immune and memory responses. In our work, we demonstrate that pre-surgical neoadjuvant immunotherapy utilizing MPS-PVP successfully mitigates residual and recurrent infections following removal of the infected implants. This study thus offers an alternative to replace antibiotics against hard-to-treat biofilm infections.

Suggested Citation

  • Chuang Yang & Yao Luo & Hao Shen & Min Ge & Jin Tang & Qiaojie Wang & Han Lin & Jianlin Shi & Xianlong Zhang, 2022. "Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32405-x
    DOI: 10.1038/s41467-022-32405-x
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    1. Yuqian Qiao & Xiangmei Liu & Bo Li & Yong Han & Yufeng Zheng & Kelvin Wai Kwok Yeung & Changyi Li & Zhenduo Cui & Yanqin Liang & Zhaoyang Li & Shengli Zhu & Xianbao Wang & Shuilin Wu, 2020. "Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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    1. Zheng Su & Dongdong Xu & Xianli Hu & Wanbo Zhu & Lingtong Kong & Zhengzheng Qian & Jiawei Mei & Ruixiang Ma & Xifu Shang & Wenpei Fan & Chen Zhu, 2024. "Biodegradable oxygen-evolving metalloantibiotics for spatiotemporal sono-metalloimmunotherapy against orthopaedic biofilm infections," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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