Awomoyi Agnes A, Marchant Arnaud, Howson Joanna M M, McAdam Keith P W J, Blackwell Jenefer M, Newport Melanie J
Medical Research Council Laboratories, Banjul, The Gambia.
J Infect Dis. 2002 Dec 15;186(12):1808-14. doi: 10.1086/345920. Epub 2002 Nov 22.
Host genetic factors are major determinants of susceptibility to tuberculosis, and an understanding of the molecular basis of this observation has major implications for the development of novel therapies and vaccines. Slc11a1 (formerly Nramp1), the first murine infection susceptibility locus identified, regulates early innate responses to intracellular pathogens. Variation in the human homologue SLC11A1 is associated with and linked to tuberculosis in genetically different populations. In a case-control study of 329 tuberculosis case patients and 324 control subjects, the association between allele 2 of a functional SLC11A1 polymorphism and tuberculosis has been reproduced. This variant is associated with higher lipopolysaccharide-induced production of the macrophage-deactivating cytokine interleukin-10. Furthermore, monocytes from persons who develop tuberculosis innately produce more interleukin-10 than do monocytes from healthy control subjects. These data therefore confirm the importance of SLC11A1 in tuberculosis susceptibility in humans and suggest that SLC11A1 influences tuberculosis susceptibility by regulation of interleukin-10.
宿主遗传因素是结核病易感性的主要决定因素，了解这一现象的分子基础对新型疗法和疫苗的开发具有重要意义。Slc11a1（以前称为Nramp1）是第一个被鉴定的小鼠感染易感性基因座，它调节对细胞内病原体的早期固有反应。人类同源基因SLC11A1的变异在遗传背景不同的人群中与结核病相关且存在连锁关系。在一项对329例结核病患者和324名对照受试者的病例对照研究中，功能性SLC11A1多态性的2等位基因与结核病之间的关联得到了重现。该变异与脂多糖诱导的巨噬细胞失活细胞因子白细胞介素-10的产生增加有关。此外，先天感染结核病的人的单核细胞比健康对照受试者的单核细胞产生更多的白细胞介素-10。因此，这些数据证实了SLC11A1在人类结核病易感性中的重要性，并表明SLC11A1通过调节白细胞介素-10影响结核病易感性。
