Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China.
School of Biomedical Engineering, Sun Yat-sen University, Guangzhou 510006, China.
Life Sci. 2021 Aug 15;279:119644. doi: 10.1016/j.lfs.2021.119644. Epub 2021 May 25.
Bacterial-derived extracellular vesicles could play a major role in attenuating and treating diseases. They play a major anti-infection role by modulating immune responses against pathogens and preventing infection by inhibiting pathogen localization and proliferation. In this study, outer membrane vesicles (ExHp-CD) released by Helicobacter pylori SS1 (H. pylori) and total antigens isolated from H. pylori SS1 (AgHp) were evaluated for their immunogenic potential and their effect on macrophage RAW 264.7 cells. Results demonstrated that both ExHp-CD and AgHp induced T helper 2 (Th2) immune response, which was reported to be important in immune protection against H. pylori infections. Both ExHp-CD and AgHp produced high levels of IL-10 and IL-4, while no significant levels of IL-12 p70 or IFN-γ were detected. However, ExHp-CD showed a better effect on macrophage RAW 264.7 cells compared to AgHp. Macrophage RAW 264.7 cells stimulated with 5, and 10 μg/mL of ExHp-CD showed an increased ratio of CD206 (M2 phenotype marker) and a decreased ratio of CD86 (M1 phenotype marker). Moreover, results suggested that the immunogenic effect that ExHp-CD possesses was attributed to their cargo of Epimerase_2 domain-containing protein (Epi_2D), Probable malate:quinone oxidoreductase (Pro_mqo), and Probable cytosol aminopeptidase (Pro_ca). Results demonstrated that ExHp-CD possesses an immunological activity to induce Th2 immune response against H. pylori infection with results comparable to AgHp. However, ExHp-CD showed higher efficacy regarding safety, biocompatibility, lack of toxicity, and hemocompatibility. Thus, it could serve as an immunogenic candidate with more desired characteristics.
细菌衍生的细胞外囊泡在减轻和治疗疾病方面可能发挥重要作用。它们通过调节针对病原体的免疫反应，防止感染通过抑制病原体的定位和增殖来发挥主要的抗感染作用。在这项研究中，评估了幽门螺杆菌 SS1（H. pylori）释放的外膜囊泡（ExHp-CD）和从 H. pylori SS1 中分离的总抗原（AgHp）的免疫原性及其对巨噬细胞 RAW 264.7 细胞的影响。结果表明，ExHp-CD 和 AgHp 均诱导辅助性 T 细胞 2（Th2）免疫反应，这被报道对免疫保护免受 H. pylori 感染很重要。ExHp-CD 和 AgHp 均产生高水平的 IL-10 和 IL-4，而未检测到显著水平的 IL-12 p70 或 IFN-γ。然而，ExHp-CD 对巨噬细胞 RAW 264.7 细胞的作用优于 AgHp。用 5 和 10 μg/mL 的 ExHp-CD 刺激的巨噬细胞 RAW 264.7 细胞显示 CD206（M2 表型标志物）的比例增加和 CD86（M1 表型标志物）的比例降低。此外，结果表明，ExHp-CD 所具有的免疫原性效应归因于其 Epimerase_2 结构域包含蛋白（Epi_2D）、可能的苹果酸：醌氧化还原酶（Pro_mqo）和可能的细胞质氨肽酶（Pro_ca）的货物。结果表明，ExHp-CD 具有诱导针对 H. pylori 感染的 Th2 免疫反应的免疫活性，其效果与 AgHp 相当。然而，ExHp-CD 在安全性、生物相容性、无毒性和血液相容性方面表现出更高的功效。因此，它可以作为一种具有更多理想特性的免疫原候选物。
