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Pathogen-derived peptidoglycan skeleton enhances innate immune defense against Staphylococcus aureus via mTOR-HIF-1α-HK2-mediated trained immunity

文献类型： 外文期刊

作者： Jia, Zheng 1 ; Niu, Lingdi 1 ; Guo, Junjie 1 ; Wang, Jiaqing 1 ; Li, Hai 1 ; Liu, Runhang 2 ; Liu, Ning 1 ; Zhang, Shuhe 1 ; Wang, Fang 2 ; Ge, Junwei 1 ;

作者机构： 1.Northeast Agr Univ, Coll Vet Med, Heilongjiang Prov Key Lab Zoonosis, Harbin 150036, Peoples R China

2.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control & Prevent, Harbin 150069, Peoples R China

关键词： Peptidoglycan skeleton; Trained immunity; Metabolic reprogramming; Innate immunity; Methicillin-resistance; Staphylococcus aureus

期刊名称：MICROBIOLOGICAL RESEARCH （ 影响因子：6.9； 五年影响因子：7.2 ）

ISSN： 0944-5013

年卷期： 2025 年 296 卷

页码：

收录情况： SCI

摘要： Regulation of the innate immune response may be an effective strategy to enhance Staphylococcus aureus vaccines. Based on our previous findings that the Listeria peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-(3 following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant S. aureus challenge and also provides protection against S. aureus CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1 alpha and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to (3-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.

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