Niu Lingdi, Duan Haoyuan, Wang Jiaqing, Jia Zheng, Li Hai, Guo Junjie, Zhang Shuhe, Liu Ning, Miao Yaxin, Ge Junwei, Wang Fang
National Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Front Immunol. 2025 Jul 18;16:1606626. doi: 10.3389/fimmu.2025.1606626. eCollection 2025.
Trained immunity refers to the ability of trained innate immune cells to generate an immune memory that produces rapid, broad-spectrum, and long-lasting protection against heterologous stimuli. Based on the rapid and broad-spectrum protection that the peptidoglycan backbone from lactic acid bacteria, bacterium-like particles (BLPs), offers, we hypothesized that BLPs enhance protection through trained immunity. Here, we found that combining BLP with a vaccine significantly improves protective efficacy against methicillin-resistant (MRSA) infection, accompanied by changes in trained immunity markers. We demonstrate that BLP-induced trained immunity macrophages exhibit increased cytokine secretion and phagocytic activity . In an model, BLP confers protection against 26003 even without specific antigens. In an model, BLP induces increased markers of trained immunity. Transcriptome analysis suggests that BLP may induce trained immunity by activating the IL-6-JAK-STAT3 pathway through TLR2 receptor activation, thereby modulating macrophage metabolic reprogramming and function. In summary, our study establishes that BLP induction of trained immunity, along with regulated metabolic reprogramming and macrophage function, may contribute to enhancing vaccine efficacy. Our findings elucidate a novel mechanism for BLP-mediated immune enhancement, critical for the application of BLP as a vaccine vector to construct a vaccine that combines specific immune response with innate immune response.
训练有素的免疫是指训练有素的先天免疫细胞产生免疫记忆的能力，这种免疫记忆能对异源刺激产生快速、广谱和持久的保护。基于乳酸菌的肽聚糖骨架、细菌样颗粒（BLP）所提供的快速和广谱保护，我们推测BLP通过训练有素的免疫增强保护作用。在此，我们发现将BLP与疫苗联合使用可显著提高对耐甲氧西林金黄色葡萄球菌（MRSA）感染的保护效果，并伴有训练有素的免疫标志物的变化。我们证明，BLP诱导的训练有素的免疫巨噬细胞表现出细胞因子分泌增加和吞噬活性增强。在一个模型中，即使没有特异性抗原，BLP也能对26003提供保护。在另一个模型中，BLP诱导训练有素的免疫标志物增加。转录组分析表明，BLP可能通过TLR2受体激活来激活IL-6-JAK-STAT3通路，从而调节巨噬细胞代谢重编程和功能，进而诱导训练有素的免疫。总之，我们的研究表明，BLP诱导训练有素的免疫以及调节代谢重编程和巨噬细胞功能，可能有助于提高疫苗效力。我们的发现阐明了BLP介导的免疫增强的新机制，这对于将BLP用作疫苗载体以构建结合特异性免疫反应与先天免疫反应的疫苗至关重要。
