Objective Bacterial translocation across the gut barrier has been implicated in the pathogenesis of SLE, though the underlying mechanisms remain unclear. This study aimed to investigate the role of translocated bacteria in the context of molecular mimicry by utilizing lupus model mice and blood samples from untreated SLE patients. Methods Bacterial translocation was evaluated using nonselective cultured mesenteric lymph nodes (MLNs) from B6SKG mice, a lupus model characterized by impaired TCR signalling and gut dysbiosis. The relationships of detected pathobionts with autoantibody production were examined using in vivo experiments, ELISA, immunoblotting and epitope mapping. Results Culture-based bacterial profiling in MLNs demonstrated that Lactobacillus murinus was enriched in B6SKG mice with elevated anti-dsDNA IgG levels. Subcutaneous injection of heat-killed L. murinus induced anti-dsDNA IgG production without altering T- or B-cell subset composition. Immunoblotting and mass spectrometry analysis identified a peptide ATP-binding cassette (ABC) transporter as a molecular mimicry antigen, with its cross-reactivity in lupus mice confirmed by serological assays and in vivo immunization. The L. murinus ABC transporter exhibited surface epitopes that were cross-reactive with sera from lupus mice and patients. The ABC transporter from R. gnavus, known for its pathogenic role in lupus patients, had a similar epitope sequence to that of the L. murinus ABC transporter and reacted with lupus sera. Conclusion ABC transporters from gut bacteria can serve as cross-reactive antigens that may promote anti-dsDNA antibody production in genetically susceptible mice. These findings underscore the role of commensal-derived molecular mimicry and bacterial translocation in lupus pathogenesis.

中文翻译：

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系统性红斑狼疮肠道共生易位与自身抗体产生的相关性


目的 细菌跨肠道屏障易位与 SLE 的发病机制有关，但其潜在机制尚不清楚。本研究旨在通过利用狼疮模型小鼠和未经治疗的 SLE 患者的血液样本来研究易位细菌在分子模拟背景下的作用。方法 使用 B6SKG 小鼠的非选择性培养肠系膜淋巴结 （MLN） 评估细菌易位，B6SKG 小鼠是一种以 TCR 信号受损和肠道菌群失调为特征的狼疮模型。使用体内实验、 ELISA 、 免疫印迹和表位定位检查检测到的致病体与自身抗体产生的关系。结果 MLNs 中基于培养的细菌分析表明，Lactobacillus murinus 在抗 dsDNA IgG 水平升高的 B6SKG 小鼠中富集。皮下注射热灭活的 L. murinus 诱导抗 dsDNA IgG 产生，而不改变 T 细胞或 B 细胞亚群组成。免疫印迹和质谱分析确定了肽 ATP 结合盒 （ABC） 转运蛋白作为分子模拟抗原，其在狼疮小鼠中的交叉反应性通过血清学测定和体内免疫证实。L. murinus ABC 转运蛋白表现出与狼疮小鼠和患者血清交叉反应的表面表位。来自 R. gnavus 的 ABC 转运蛋白以其在狼疮患者中的致病作用而闻名，具有与 L. murinus ABC 转运蛋白相似的表位序列，并与狼疮血清反应。结论 肠道细菌的 ABC 转运蛋白可以作为交叉反应抗原，可促进遗传易感小鼠产生抗 dsDNA 抗体。 这些发现强调了共生来源的分子模拟和细菌易位在狼疮发病机制中的作用。