Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis
Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis
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DOI：
10.1016/j.tube.2015.02.045
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发表时间：
2015-05-01
期刊：
影响因子：
3.2
通讯作者：
Conrad, Melanie L.
中科院分区：
文献类型：
--
作者：
Dittrich, Nickel;Berrocal-Almanza, Luis C.;Conrad, Melanie L.
背景：结核（TB）是由结核分枝杆菌（MTB）感染引起的一种疾病，仍然是一个全球性的公共卫生问题。感染个体对结核的易感性差异很大，先天免疫系统对分枝杆菌的识别可能影响疾病的过程和结果。这项研究描述了toll样受体（TLR） 1基因的单核苷酸多态性，该基因在功能上改变了对MTB的先天免疫反应，并与印度的结核病易感性有关。方法：对来自印度海得拉巴的206例结核病患者和239名健康对照者的TLR1和TLR2基因snp进行分析，这些基因随后与结核病易感性相关。为了测试个体对MTB裂解物的反应，我们刺激了来自基因分型的健康德国个体的pbmc，以及转染了TLR1/2变体的HEK细胞。分别测定TNF的产生和NF-kappa B的活化。结果：队列分析表明TLR1-248N SNP （RS4833095）与TB保护相关。健康对照中表达TLR1-248N的PBMCs对MTB裂解物表现出更高的TNF反应。除此之外，用转染TLR1-248N和MTB刺激的HEK细胞系进行的功能研究显示，NF-kappa B活化增加。结论：SNP TLR1-248N在印度人群中与结核病保护有关，并且在体外对MTB裂解物表现出增强的免疫应答。(C) 2015 Elsevier Ltd.版权所有。
Background: Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (MTB) infection, is still a global public health problem. TB susceptibility varies greatly in infected individuals, and mycobacterial recognition by the innate immune system likely affects disease course and outcome. This research describes a single nucleotide polymorphism in the Toll-like receptor (TLR) 1 gene that functionally alters the innate immune response to MTB and is associated with TB susceptibility in India.Methods: 206 TB patients and 239 healthy controls from Hyderabad, India were analyzed for SNPs in the TLR1 and TLR2 genes, which were subsequently correlated to TB susceptibility. To test individual responses to MTB lysates, we stimulated PBMCs from genotyped healthy German individuals, as well as HEK cells transfected with TLR1/2 variants. TNF production and NF-kappa B activation were assessed respectively.Results: Cohort analysis associated the TLR1-248N SNP (RS4833095) with TB protection. TLR1-248N expressing PBMCs from healthy controls exhibited an increased TNF response to MTB lysates. In addition to this, functional studies using HEK cell lines transfected with TLR1-248N and stimulated with MTB showed an increased NF-kappa B activation.Conclusion: SNP TLR1-248N is associated with TB protection in an Indian population and exhibits an increased immune response to MTB lysate in vitro. (C) 2015 Elsevier Ltd. All rights reserved.