Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus.

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B Streptococcus.
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DOI:
10.1007/s00109-014-1157-y
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发表时间:
2014-09
影响因子:
4.7
通讯作者:
Nizet, Victor
Nizet, Victor
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Yung-Chi;Olson, Joshua;Louie, Aaron;Crocker, Paul R.;Varki, Ajit;Nizet, Victor

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几种细菌病原体用细胞壁成分或荚膜外多糖内的唾液酸残基修饰其表面。唾液酸的表达可以通过阻断补体激活或抑制唾液酸结合免疫球蛋白样凝集素(Siglecs)对宿主白细胞的作用来促进细菌的毒力。唾液粘附素(Sn)在脾和淋巴结巨噬细胞中高水平表达,是一种独特的Siglec,具有细长的结构,缺乏细胞内信号基元。唾液粘附素允许巨噬细胞参与某些唾液化病原体并刺激炎症反应,但唾液粘附素在体内感染中的意义尚未得到证实。我们证明了巨噬细胞吞噬唾液化的病原体B族链球菌(GBS),并通过唾液粘附素-唾液酸介导的识别增加杀菌活性。脾脏边缘区嗜金属巨噬细胞上唾液粘附素的表达可以阻滞循环中的GBS,限制GBS向远处器官的扩散,降低死亡率。唾液黏附素缺乏小鼠对GBS攻击的特异性IgM抗体反应也受损。因此,唾液粘附素是协调先天和适应性免疫防御入侵唾液化细菌病原体的关键桥梁。唾液粘附素对巨噬细胞吞噬和清除GBS至关重要。唾液黏附素缺乏小鼠GBS器官播散增加。减少唾液黏附素缺乏小鼠抗gbs IgM的产生。本文的在线版本(doi:10.1007/s00109-014-1157-y)包含补充材料,仅供授权用户使用。
Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users.
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