Bowker Nicholas, Salie Muneeb, Schurz Haiko, van Helden Paul D, Kinnear Craig J, Hoal Eileen G, Möller Marlo
SA MRC Centre for TB Research, DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Teaching Building, 4th Floor, Room 4036, Tygerberg, Cape Town, 7505, South Africa.
Lung. 2016 Oct;194(5):763-7. doi: 10.1007/s00408-016-9915-y. Epub 2016 Jun 30.
The mechanisms involved in interactions between Mycobacterium tuberculosis and host innate immune cells determine outcome. Antigen-presenting cells, including macrophages and dendritic cells, express many pattern recognition receptors to identify pathogen-associated molecular patterns, thereby initiating an immune response. A major mycobacterial virulence factor, trehalose-6',6-dimycolate, is recognised by the macrophage-inducible C-type lectin, Mincle, which leads to the activation of the Syk-Card9 signalling pathway in macrophages. Mincle is encoded by CLEC4E, and we investigated polymorphisms in this gene to assess its role in tuberculosis susceptibility. Four tagging single nucleotide polymorphisms (SNPs) (rs10841845, rs10841847, rs10841856 and rs4620776) were genotyped using TaqMan(®) SNP assays in 416 tuberculosis cases and 405 healthy controls. Logistic regression models were used for analysis. No association was detected with any of the SNPs analysed. This research highlights tuberculosis disease complexity where recognition proteins which specifically bind mycobacterial glycolipids cannot be conclusively associated with the disease in genetic studies.
结核分枝杆菌与宿主固有免疫细胞之间相互作用所涉及的机制决定了疾病的转归。包括巨噬细胞和树突状细胞在内的抗原呈递细胞表达多种模式识别受体，以识别病原体相关分子模式，从而启动免疫反应。一种主要的分枝杆菌毒力因子，海藻糖-6',6-二霉菌酸酯，可被巨噬细胞诱导性C型凝集素Mincle识别，这会导致巨噬细胞中Syk-Card9信号通路的激活。Mincle由CLEC4E编码，我们研究了该基因中的多态性，以评估其在结核病易感性中的作用。使用TaqMan(®)SNP分析对416例结核病患者和405名健康对照进行了4个标签单核苷酸多态性（SNP）（rs10841845、rs10841847、rs10841856和rs4620776）的基因分型。采用逻辑回归模型进行分析。在所分析的任何SNP中均未检测到关联。这项研究突出了结核病的疾病复杂性，即在遗传研究中，与分枝杆菌糖脂特异性结合的识别蛋白不能最终与该疾病相关联。
