McMaster Immunology Research Centre, McMaster University, Hamilton, ON, L8S 4K1, Canada.
BMC Med Genet. 2013 Apr 23;14:47. doi: 10.1186/1471-2350-14-47.
The two major class A scavenger receptors are scavenger receptor A (SRA), which is constitutively expressed on most macrophage populations, and macrophage receptor with collagenous structure (MARCO), which is constitutively expressed on a more restricted subset of macrophages, (e.g. alveolar macrophages) but whose expression increases on most macrophages during the course of infection. Although the primary role of SRA appears to be clearance of modified host proteins and lipids, mice defective in expression of either MARCO or SRA are immunocompromised in multiple models of infection and in vitro assays, the scavenger receptors have been demonstrated to bind bacteria and to enhance pro-inflammatory signalling to many bacterial lung pathogens; however their importance in Mycobacterium tuberculosis infection, is less clear.
To determine whether polymorphisms in either SRA or MARCO were associated with tuberculosis, a case-control study of was performed. DNA samples from newly-detected, smear-positive, pulmonary tuberculosis cases were collected from The Gambia. Controls for this study consisted of DNA from cord bloods obtained from routine births at local Gambian health clinics. Informed written consent was obtained from patients or their parents or guardians. Ethical approval was provided by the joint The Gambian Government/MRC Joint Ethics Committee.
We studied the frequencies of 25 polymorphisms of MSR1 (SRA) and 22 in MARCO in individuals with tuberculosis (n=1284) and matched controls (n=1349). No SNPs within the gene encoding or within 1 kb of the promoter sequence of MSR1 were associated with either susceptibility or resistance to tuberculosis. Three SNPs in MARCO (rs4491733, Mantel-Haenszel 2x2 χ2 = 6.5, p = 0.001, rs12998782, Mantel-Haenszel 2x2 χ2 = 6.59, p = 0.001, rs13389814 Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) were associated with susceptibility to tuberculosis and one (rs7559955, Mantel-Haenszel 2x2 χ2 = 6.9, p = 0.0009) was associated with resistance to tuberculosis.
These findings identify MARCO as a potentially important receptor in the host response to tuberculosis.
两种主要的 A 类清道夫受体是清道夫受体 A（SRA），它在大多数巨噬细胞群体中持续表达，以及具有胶原结构的巨噬细胞受体（MARCO），它在更受限制的巨噬细胞亚群中持续表达（例如肺泡巨噬细胞），但在感染过程中大多数巨噬细胞的表达增加。尽管 SRA 的主要作用似乎是清除修饰的宿主蛋白和脂质，但在多种感染模型和体外测定中，MARCO 或 SRA 表达缺陷的小鼠在感染和体外测定中免疫功能受损，已证明清道夫受体可结合细菌并增强许多肺部细菌病原体的促炎信号；然而，它们在结核分枝杆菌感染中的重要性不太清楚。
为了确定 SRA 或 MARCO 中的多态性是否与结核病相关，进行了一项病例对照研究。从冈比亚新发现的、涂片阳性的肺结核病例中采集 DNA 样本。本研究的对照来自当地冈比亚诊所常规分娩的脐带血 DNA。患者或其父母或监护人获得了知情书面同意。联合冈比亚政府/MRC 联合伦理委员会提供了伦理批准。
我们研究了 1284 例结核病患者和 1349 例匹配对照个体中 MSR1（SRA）的 25 个多态性和 MARCO 中的 22 个多态性的频率。编码基因内或启动子序列 1 kb 内的 MSR1 没有 SNP 与结核病的易感性或耐药性相关。MARCO 中的三个 SNP（rs4491733、Mantel-Haenszel 2x2 χ2 = 6.5，p = 0.001，rs12998782，Mantel-Haenszel 2x2 χ2 = 6.59，p = 0.001，rs13389814 Mantel-Haenszel 2x2 χ2 = 6.9，p = 0.0009）与结核病易感性相关，一个（rs7559955，Mantel-Haenszel 2x2 χ2 = 6.9，p = 0.0009）与结核病耐药性相关。
这些发现表明 MARCO 是宿主对结核病反应中的一个潜在重要受体。
