Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake
Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake
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DOI：
10.1046/j.1365-2958.2003.03634.x
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发表时间：
2003-09-01
影响因子：
3.6
通讯作者：
Crocker, PR
中科院分区：
文献类型：
--
作者：
Jones, C;Virji, M;Crocker, PR
唾液酸结合免疫球蛋白样凝集素 (siglecs) 主要在造血和免疫系统中表达，并且对 N-聚糖、O-聚糖和糖脂中唾液酸的连接和性质表现出特异性。几种 siglec，包括 sialoadhesin (Sn、siglec-1) 和 siglec-5，与 NeuAc a 2,3Gal 结合，NeuAc a 2,3Gal 是一种末端加帽结构，也可以显示在脑膜炎奈瑟菌 (Nm) 的脂多糖 (LPS) 上。在本研究中，我们检查了免疫系统细胞上表达的 siglecs 作为唾液酸化 Nm 受体的潜力。在这项研究中，我们使用了 Nm 两个血清群（A 和 B）的唾液酸化和非唾液酸化 LPS 衍生物。使用重组嵌合可溶性受体、siglec 转染的细胞系和来自野生型和 Sn 缺陷小鼠的巨噬细胞，我们观察到任一遗传背景的唾液酸化变体都能被 Sn 和 siglec-5 特异性识别，而检查的其他 siglec 则无效。此外，表达Sn的巨噬细胞以及表达Sn或siglec-5的转染子以siglec和唾液酸依赖性方式结合并吞噬唾液酸化细菌。这项研究表明，Nm LPS 唾液酸化可导致细菌对吞噬细胞摄取的敏感性增加，这一现象与之前报道的 LPS 唾液酸化的保护作用形成鲜明对比。
Sialic acid-binding immunoglobulin-like lectins (siglecs) are expressed predominantly in the haemopoietic and immune systems and exhibit specificities for both the linkage and the nature of sialic acids in N-glycans, O-glycans and glycolipids. Several siglecs, including sialoadhesin (Sn, siglec-1) and siglec-5, bind to NeuAc a 2,3Gal, a terminal capping structure that can also be displayed on the lipopolysaccharide (LPS) of Neisseria meningitidis (Nm). In the present study, we examined the potential of siglecs expressed on cells of the immune system to function as receptors for sialylated Nm. We used sialylated and non-sialylated LPS derivatives of two serogroups (A and B) of Nm in this study. Using recombinant chimeric soluble receptors, siglec-transfected cell lines and macrophages from wildtype and Sn-deficient mice, we observed that sialylated but not non-sialylated variants of either genetic background were specifically recognized by Sn and siglec-5, whereas other siglecs examined were ineffective. In addition, macrophages expressing Sn, as well as transfectants expressing Sn or siglec-5, bound and phagocytosed sialylated bacteria in a siglec-and sialic acid-dependent manner. This study demonstrates that Nm LPS sialylation can lead to increased bacterial susceptibility to phagocytic uptake, a phenomenon in direct contrast to previously reported protective effects of LPS sialylation.