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

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.

SUBMITTER: Yang C

PROVIDER: S-EPMC9388665 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Yang Chuang C Luo Yao Y Shen Hao H Ge Min M Tang Jin J Wang Qiaojie Q Lin Han H Shi Jianlin J Zhang Xianlong X

Nature communications 20220818 1

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 MnPSe<sub>3</sub> (MPS) nanosheets modified with polyvinylpyrrolidone (PVP) are capable of triggering a strong anti-bacterial biof ...[more]

PMID: 35982036

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

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

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