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

Chuang Yang, Yao Luo, Hao Shen, Min Ge, Jin Tang, Qiaojie Wang, Han Lin (), Jianlin Shi () and Xianlong Zhang ()
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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

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32405-x

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