Langerhans cells are key sentinel cells of the skin and mucosal lining. They sense microorganisms through their repertoire of pattern-recognition receptors to mount and direct appropriate immune responses. We recently demonstrated that human Langerhans cells interact with the Gram-positive pathogen Staphylococcus aureus through the Langerhans cell-specific receptor langerin (CD207). It was previously hypothesized that two linked single nucleotide polymorphisms (SNPs; N288D and K313I) in the carbohydrate recognition domain of langerin would affect interaction with microorganisms. We show that recognition of S. aureus by recombinant langerin molecules is abrogated in the co-inheriting SNP variant, which is mainly explained by the N288D SNP and further enhanced by K313I. Moreover, introduction of SNP N288D in ectopically-expressed langerin affected cellular distribution of the receptor such that langerin displayed enhanced plasma membraneexpression. Despite this increased binding of S. aureus by the langerin double SNP variant, uptake of bacteria by this langerin variant was compromised. Our findings indicate that in a proportion of the human population, the recognition and uptake of S. aureus by Langerhans cells may be affected, which could have important consequences for proper immune activation and S. aureus-associated disease.

中文翻译：

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Langerin (CD207) 的常见遗传变异会影响金黄色葡萄球菌的细胞摄取。

朗格汉斯细胞是皮肤和粘膜内层的关键哨兵细胞。它们通过它们的模式识别受体库感知微生物，以启动和引导适当的免疫反应。我们最近证明了人类朗格汉斯细胞通过朗格汉斯细胞特异性受体朗格蛋白 (CD207) 与革兰氏阳性病原体金黄色葡萄球菌相互作用。先前假设兰芝糖识别域中的两个连接的单核苷酸多态性（SNP；N288D 和 K313I）会影响与微生物的相互作用。我们表明重组 langerin 分子对金黄色葡萄球菌的识别在共同遗传的 SNP 变体中被废除，这主要由 N288D SNP 解释并由 K313I 进一步增强。而且，在异位表达的 langerin 中引入 SNP N288D 影响了受体的细胞分布，使得 langerin 显示出增强的质膜表达。尽管 langerin 双 SNP 变体增加了金黄色葡萄球菌的结合，但这种 langerin 变体对细菌的吸收受到了损害。我们的研究结果表明，在一定比例的人群中，朗格汉斯细胞对金黄色葡萄球菌的识别和摄取可能会受到影响，这可能对适当的免疫激活和金黄色葡萄球菌相关疾病产生重要影响。