Berrington William R, Hawn Thomas R
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195-0001, USA.
Immunol Rev. 2007 Oct;219:167-86. doi: 10.1111/j.1600-065X.2007.00545.x.
Despite the discovery of the tuberculosis (TB) bacillus over 100 years ago and the availability of effective drugs for over 50 years, there remain a number of formidable challenges for controlling Mycobacterium tuberculosis (MTb). Understanding the genetic and immunologic factors that influence human susceptibility could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease. Although a series of studies over the past 50 years suggests that host genetics influences resistance to TB, a comprehensive understanding of which genes and variants are associated with susceptibility is only partially understood. In this article, we review recent advances in our understanding of human variation of the immune system and its effects on macrophage function and influence on MTb susceptibility. We emphasize recent discoveries in human genetic studies and correlate these findings with efforts to understand how these variants alter the molecular and cellular functions that regulate the macrophage response to MTb.
尽管100多年前就发现了结核杆菌，且50多年来一直有有效的药物，但在控制结核分枝杆菌（MTb）方面仍存在许多艰巨的挑战。了解影响人类易感性的遗传和免疫因素，可能会为疫苗开发带来新的见解，并推动诊断进展，以便针对有发展为活动性疾病风险的人群进行靶向治疗。尽管过去50年的一系列研究表明宿主基因会影响对结核病的抵抗力，但对于哪些基因和变体与易感性相关的全面理解仍仅处于部分认知阶段。在本文中，我们回顾了我们对人类免疫系统变异及其对巨噬细胞功能的影响以及对MTb易感性的影响的最新认识进展。我们着重介绍了人类遗传学研究中的最新发现，并将这些发现与理解这些变体如何改变调节巨噬细胞对MTb反应的分子和细胞功能的研究成果相关联。
