Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Infect Immun. 2013 Jun;81(6):2095-103. doi: 10.1128/IAI.01437-12. Epub 2013 Mar 25.
Molecular mimicry between Campylobacter jejuni sialylated lipooligosaccharides (LOS) and human nerve gangliosides can trigger the production of cross-reactive antibodies which induce Guillain-Barré syndrome (GBS). To better understand the immune events leading to GBS, it is essential to know how sialylated LOS are recognized by the immune system. Here, we show that GBS-associated C. jejuni strains bind to human sialoadhesin (hSn), a conserved, mainly macrophage-restricted I-type lectin. Using hSn-transduced THP-1 cells, we observed that C. jejuni strains with α(2,3)-sialylated LOS, including strains expressing GM1a- and GD1a-like epitopes, bind to hSn. This observation is of importance, as these epitopes are frequently the targets of the cross-reactive antibodies detected in GBS patients. Interestingly, the Sn binding domains were not constitutively exposed on the surface of C. jejuni. Heat inactivation and the environmental conditions which food-borne C. jejuni encounters during its passage through the intestinal tract, such as low pH and contact with bile constituents, exposed LOS and facilitated Sn binding. Sn binding enhanced bacterial uptake and increased the production of interleukin-6 (IL-6) by primary human Sn-expressing monocyte-derived macrophages compared to control conditions, where Sn was blocked using neutralizing antibodies or when nonsialylated C. jejuni was used. Sn-mediated uptake has been reported to enhance humoral immune responses. As C. jejuni strains expressing ganglioside mimics GD1a and GM1a are closely associated with GBS, Sn binding may be a determining event in the production of cross-reactive antibodies and the development of GBS.
空肠弯曲菌唾液酸化脂寡糖（LOS）与人神经节苷脂之间的分子模拟可触发产生交叉反应性抗体，从而引起格林-巴利综合征（GBS）。为了更好地了解导致 GBS 的免疫事件，了解唾液酸化 LOS 如何被免疫系统识别至关重要。在这里，我们表明与 GBS 相关的空肠弯曲菌菌株与人类唾液酸粘附素（hSn）结合，hSn 是一种保守的、主要在巨噬细胞中受限的 I 型凝集素。使用转染 hSn 的 THP-1 细胞，我们观察到具有α（2,3）-唾液酸化 LOS 的空肠弯曲菌菌株，包括表达 GM1a 和 GD1a 样表位的菌株，与 hSn 结合。这一观察结果很重要，因为这些表位是 GBS 患者中检测到的交叉反应性抗体的常见靶标。有趣的是，Sn 结合结构域在空肠弯曲菌表面并非始终暴露。热失活以及食源性病原体空肠弯曲菌在通过肠道时遇到的环境条件，如低 pH 值和与胆汁成分接触，暴露 LOS 并促进 Sn 结合。与对照条件相比，Sn 结合增强了细菌摄取并增加了人源 Sn 表达单核细胞衍生巨噬细胞中白细胞介素-6（IL-6）的产生，对照条件中使用了中和抗体阻断 Sn 或使用非唾液酸化的空肠弯曲菌。据报道，Sn 介导的摄取可增强体液免疫反应。由于表达神经节苷脂模拟物 GD1a 和 GM1a 的空肠弯曲菌菌株与 GBS 密切相关，因此 Sn 结合可能是产生交叉反应性抗体和发展 GBS 的决定性事件。
