Pneumococcal vaccination decreases atherosclerotic lesion formation:: molecular mimicry between Streptococcus pneumoniae and oxidized LDL
Pneumococcal vaccination decreases atherosclerotic lesion formation:: molecular mimicry between Streptococcus pneumoniae and oxidized LDL
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DOI：
10.1038/nm876
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发表时间：
2003-06-01
期刊：
影响因子：
82.9
通讯作者：
Silverman, GJ
中科院分区：
文献类型：
--
作者：
Binder, CJ;Hörkkö, S;Silverman, GJ
在动脉粥样硬化的进展过程中，自身抗体被诱导氧化低密度脂蛋白（oxLDL）的表位和高胆固醇血症小鼠的oxLDL主动免疫改善动脉粥样硬化的形成。我们意外地发现，许多来自“幼稚”动脉粥样硬化小鼠的oxLDL自身抗体与来自经典抗磷酸胆碱B细胞克隆T15的抗体具有完全的遗传和结构同一性，T15可保护免受常见感染性病原体，包括肺炎球菌。为了研究体内暴露于肺炎球菌是否会影响动脉粥样硬化形成，我们用肺炎链球菌免疫Ldlr（-/-）小鼠。这诱导了高循环水平的oxLDL特异性IgM和主要在脾脏中的oxLDL特异性T15 IgM分泌B细胞的持续扩增，其与肺炎球菌决定簇交叉反应。肺炎球菌免疫降低了动脉粥样硬化的程度，这些小鼠的血浆具有增强的阻断oxLDL与巨噬细胞结合的能力。这些研究表明oxLDL和S.肺炎，并表明这些免疫应答可以具有有益的效果。
During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis. We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci. To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae. This induced high circulating levels of oxLDL-specific IgM and a persistent expansion of oxLDL-specific T15 IgM-secreting B cells primarily in the spleen, which were cross-reactive with pneumococcal determinants. Pneumococcal immunization decreased the extent of atherosclerosis, and plasma from these mice had an enhanced capacity to block the binding of oxLDL to macrophages. These studies show molecular mimicry between epitopes of oxLDL and S. pneumoniae and indicate that these immune responses can have beneficial effects.