ORIGINAL RESEARCH article
Front. Immunol.
Sec. Immunological Memory
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1606626
This article is part of the Research TopicMolecular and Genomics Approaches to Understanding Innate Immune MemoryView all articles
Probiotic Peptidoglycan Skeleton Enhances Vaccine Efficacy Against MRSA by Inducing Trained Immunity via the TLR2/JAK-STAT3 Pathway
Provisionally accepted
Lingdi Niu1,2
Haoyuan Duan1Jiaqing Wang1Zheng Jia1Hai Li1Junjie Guo1Shuhe Zhang1Ning Liu1Yaxin Miao1
Junwei Ge1*
Fang Wang2*- 1Northeast Agricultural University, Harbin, China
- 2State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute (CAAS), Harbin, Heilongjiang Province, China
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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 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 vitro. In an in vivo model, BLP confers protection against Staphylococcus aureus 26003 even without specific antigens. In an ex vivo 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.
Keywords: Peptidoglycan backbone, Bacterium-Like Particles, innate immunity, trained immunity, MRSA
Received: 06 Apr 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Niu, Duan, Wang, Jia, Li, Guo, Zhang, Liu, Miao, Ge and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Junwei Ge, Northeast Agricultural University, Harbin, China
Fang Wang, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute (CAAS), Harbin, 150001, Heilongjiang Province, China
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