Department of Oral Microbiology and Immunology, and Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea.
Department of Agricultural Biotechnology, and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Mol Immunol. 2024 Jan;165:82-91. doi: 10.1016/j.molimm.2023.12.009. Epub 2023 Dec 30.
Dendritic cells (DCs) play an important role in immunity by sensing and responding to invasive microbes. Bacillus species are rod-shaped sporulating bacteria that include the pathogenic Bacillus cereus and commensal Bacillus subtilis. Although the interaction between DC and these two Bacillus species has been studied, their key structural component that prompts DC activation is poorly understood. Here, we investigated the two Bacillus species in DC activation by whole cells and their representative microbe-associated molecular patterns (MAMPs). MAMPs including lipoteichoic acid (LTA), lipoprotein (LPP), and peptidoglycan (PGN) were purified from the two Bacillus species. Among the MAMPs, LPP from both species most potently induced the maturation and activation of DCs while PGN, but not LTA, moderately stimulated DCs. LPPs from both Bacillus species enhanced the expression of DC maturation markers including CCR7, CD40, CD80, CD83, CD86, CD205, MHC-I, and MHC-II. Among the MAMPs from B. cereus, PGN most considerably lowered the endocytic capacity of DCs implying DC maturation whereas PGN from B. subtilis lowered it to a similar degree to its LPP. Furthermore, DCs sensitized with LPPs from both Bacillus species and PGN from B. subtilis moderately induced TNF-α and IL-6 production. Notably, a combination of MAMPs did not show any synergistic effect on DC activation. Taken together, our results demonstrate that LPP is the key structural component in B. cereus and B. subtilis that leads to DC activation.
树突状细胞 (DCs) 通过感应和响应入侵微生物在免疫中发挥重要作用。芽孢杆菌属是一种杆状产芽孢细菌,包括致病菌蜡状芽孢杆菌和共生枯草芽孢杆菌。尽管已经研究了 DC 与这两种芽孢杆菌的相互作用,但它们促使 DC 激活的关键结构成分仍知之甚少。在这里,我们研究了这两种芽孢杆菌通过全细胞及其代表性微生物相关分子模式 (MAMPs) 对 DC 的激活作用。从这两种芽孢杆菌中纯化了脂磷壁酸 (LTA)、脂蛋白 (LPP) 和肽聚糖 (PGN) 等 MAMPs。在这些 MAMPs 中,两种细菌的 LPP 最有效地诱导了 DC 的成熟和激活,而 PGN 仅适度刺激了 DC。两种芽孢杆菌的 LPP 增强了 DC 成熟标志物的表达,包括 CCR7、CD40、CD80、CD83、CD86、CD205、MHC-I 和 MHC-II。在来自蜡状芽孢杆菌的 MAMPs 中,PGN 极大地降低了 DC 的内吞能力,暗示 DC 成熟,而来自枯草芽孢杆菌的 PGN 则将其降低到与其 LPP 相似的程度。此外,用来自两种芽孢杆菌的 LPP 和来自枯草芽孢杆菌的 PGN 敏化的 DC 适度诱导了 TNF-α 和 IL-6 的产生。值得注意的是,MAMPs 的组合对 DC 激活没有任何协同作用。总之,我们的研究结果表明,LPP 是导致 DC 激活的蜡状芽孢杆菌和枯草芽孢杆菌的关键结构成分。