The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, United Kingdom.
The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, United Kingdom ; MRC Centre for Transplantation, King's College London, London, United Kingdom.
PLoS One. 2013 Dec 13;8(12):e81056. doi: 10.1371/journal.pone.0081056. eCollection 2013.
To investigate the antigenic effect of a peptide containing two epitopes of Chlamydia pneumoniae (Cpn) on atherosclerotic lesion formation in mice infected with Cpn.
Six-week-old Apob(tm2Sgy)Ldlr(tm1Her)/J mice were immunized using a repetitive immunization multiple-sites strategy with KLH-conjugated peptides derived from the major outer membrane protein and the putative outer membrane protein 5 of Cpn. Mice were fed a high-fat diet and infected with Cpn twice during the 10-week diet period. Lesions were evaluated histologically; local and systemic immune responses were analyzed by immunohistochemistry of aorta samples and cytokine measurements in plasma samples and splenocyte supernatants.
Mice immunized with the combined Cpn peptide showed a greater reduction in lesion size compared to mice immunized with either epitope alone [54.7% vs 39.8% or 41.72%] and was also associated with a significant decrease in lesion area in descending aortas compared with those in controls (88.9% for combined Cpn peptide, 81.9% for MOMP peptide and 75.7% for Omp5, respectively). This effect was associated with a shift in the cellular composition of plaques towards decreased inflammatory cell and increased regulatory T-cell content. Additionally, the effect was also connected with decreased secretion of proinflammatory cytokines and increased production of anti-inflammatory cytokines demonstrated in plasma and in supernatant on stimulated spleen cells.
Atherosclerotic lesion formation may be promoted by Cpn infection in the presence of a high-fat diet, and reduced by immunization with the combined Cpn peptide. The combined peptide has more potential than either epitope alone in reducing atherosclerotic lesion development through Treg expansion.
研究含有肺炎衣原体（Cpn）两个表位的肽对感染 Cpn 的小鼠动脉粥样硬化病变形成的抗原作用。
采用 KLH 缀合的 Cpn 主要外膜蛋白和假定外膜蛋白 5 肽，对 6 周龄 Apob(tm2Sgy)Ldlr(tm1Her)/J 小鼠进行重复免疫多点策略免疫。在 10 周饮食期间，给予高脂饮食并两次感染 Cpn。通过组织病理学评估病变；通过主动脉样本的免疫组织化学分析和血浆样本及脾细胞上清液中细胞因子的测量分析局部和全身免疫反应。
与单独免疫任一表位的小鼠相比，联合 Cpn 肽免疫的小鼠的病变大小减少更大[54.7%比 39.8%或 41.72%]，与对照组相比，降主动脉的病变面积也显著减少（联合 Cpn 肽为 88.9%，MOMP 肽为 81.9%，Omp5 为 75.7%）。这种效果与斑块中细胞成分向炎症细胞减少和调节性 T 细胞增加的转变有关。此外，这种效果还与在刺激脾细胞的血浆和上清液中观察到的促炎细胞因子减少和抗炎细胞因子增加有关。
在高脂肪饮食存在的情况下，Cpn 感染可能会促进动脉粥样硬化病变的形成，而用联合 Cpn 肽免疫则会减少。与单独使用任一表位相比，联合肽在通过 Treg 扩增减少动脉粥样硬化病变发展方面具有更大的潜力。
