Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes
Group B streptococcal capsular sialic acids interact with siglecs (immunoglobulin-like lectins) on human leukocytes
复制标题
DOI：
10.1128/jb.01155-06
复制
发表时间：
2007-02-01
影响因子：
3.2
通讯作者：
Nizet, Victor
中科院分区：
文献类型：
--
作者：
Carlin, Aaron F.;Lewis, Amanda L.;Nizet, Victor
B 族链球菌 (GBS) 分为九种血清型，它们的荚膜多糖 (CPS) 结构各不相同，但都存在末端唾液酸 (Sia) 残基。 GBS Sia 的这种位置和连接与人类细胞中大量存在的细胞表面聚糖的位置和连接非常相似。 CD33 相关的 Siglecs (CD33rSiglecs) 是在宿主白细胞上表达的 Sia 结合凝集素家族，它与宿主 Sia 加帽的聚糖结合并发送抑制炎症基因激活的信号。我们假设 GBS 进化为将 CPS Sia 显示为一种限制有效先天免疫反应激活的分子拟态形式。在这项研究中，我们应用了一组免疫学和基于细胞的检测来证明几种血清型的 GBS 以 Sia 和血清型特异性方式与某些人类 CD33rSiglecs 相互作用，包括中性粒细胞和单核细胞上表达的 hSiglec-9 和 hSiglec-5。最近已经认识到 O 乙酰化对 GBS CPS Sia 的修饰，并且我们进一步表明 O 乙酰化程度可以显着影响 GBS 与 hSiglec-5、-7 和 -9 之间的相互作用。因此，模拟人细胞表面聚糖以接合 CD33rSiglecs 的 Sia 封端细菌多糖胶囊的生产可能是以前未被认识的白细胞操纵细菌机制的一个例子。
Group B Streptococcus (GBS) is classified into nine serotypes that vary in capsular polysaccharide (CPS) architecture but share in common the presence of a terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely resembles that of cell surface glycans found abundantly on human cells. CD33-related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on host leukocytes that engage host Sia-capped glycans and send signals that dampen inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia as a form of molecular mimicry limiting the activation of an effective innate immune response. In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia- and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by O acetylation has recently been recognized, and we further show that the degree of O acetylation can markedly affect the interaction between GBS and hSiglec-5, -7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation.