Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy
Cutting edge: A common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy
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DOI：
10.4049/jimmunol.178.12.7520
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发表时间：
2007-06-15
影响因子：
4.4
通讯作者：
Tapping, Richard I.
中科院分区：
文献类型：
--
作者：
Johnson, Christopher M.;Lyle, Elizabeth A.;Tapping, Richard I.
TLR构成模式识别分子的基本家族，其通过直接识别保守的微生物组分，在感染后引发炎症反应。在这一作用中，TLR1使宿主能够对各种细菌产生反应，包括分枝杆菌的致病性物种。在这项研究中，我们报告说，I602S，TLR1内的一个常见的单核苷酸多态性，与异常贩运的受体的细胞表面和减少血液单核细胞对细菌激动剂的反应。当在异源系统中表达时，TLR1 602S变体而不是TLR1 6021变体表现出预期的运输和响应性缺陷。在白色欧洲人中，602 S等位基因代表了迄今为止鉴定的影响TLR功能的最常见的单核苷酸多态性。令人惊讶的是，602S等位基因与麻风病发病率降低相关，表明麻风分枝杆菌破坏了TLR系统作为免疫逃避机制。
TLRs constitute an essential family of pattern recognition molecules that, through direct recognition of conserved microbial components, initiate inflammatory responses following infection. In this role, TLR1, enables host responses to a variety of bacteria, including pathogenic species of mycobacteria. In this study, we report that I602S, a common single nucleotide polymorphism within TLR1, is associated with aberrant trafficking of the receptor to the cell surface and diminished responses of blood monocytes to bacterial agonists. When expressed in heterologous systems, the TLR1 602S variant, but not the TLR1 6021 variant, exhibits the expected deficiencies in trafficking and responsiveness. Among white Europeans, the 602S allele represents the most common single nucleotide polymorphism affecting TLR function identified to date. Surprisingly, the 602S allele is associated with a decreased incidence of leprosy, suggesting that Mycobacterium leprae subverts the TLR system as a mechanism of immune evasion.