Yu Elaine A, John Serene H, Tablante Elizabeth C, King Christine A, Kenneth John, Russell David G, Mehta Saurabh
Division of Nutritional Sciences, Cornell University, Ithaca, New York, United States.
Division of Infectious Diseases, St. John's Research Institute, Bangalore, Karnataka, India.
PLoS One. 2017 Oct 4;12(10):e0185640. doi: 10.1371/journal.pone.0185640. eCollection 2017.
The identification of immune correlates that are predictive of disease outcome for tuberculosis remains an ongoing challenge. To address this issue, we evaluated gene expression profiles from peripheral blood mononuclear cells following ex vivo challenge with Mycobacterium tuberculosis, among participants with active TB disease (ATBD, n = 10), latent TB infection (LTBI, n = 10), and previous active TB disease (after successful treatment; PTBD, n = 10), relative to controls (n = 10). Differential gene expression profiles were assessed by suppression-subtractive hybridization, dot blot, real-time polymerase chain reaction, and the comparative cycle threshold methods. Comparing ATBD to control samples, greater fold-increases of gene expression were observed for a number of chemotactic factors (CXCL1, CXCL3, IL8, MCP1, MIP1α). ATBD was also associated with higher IL1B gene expression, relative to controls. Among LTBI samples, gene expression of several chemotactic factors (CXCL2, CXCL3, IL8) was similarly elevated, compared to individuals with PTBD. Our results demonstrated that samples from participants with ATBD and LTBI have distinct gene expression profiles in response to ex vivo M. tuberculosis infection. These findings indicate the value in further characterizing the peripheral responses to M. tuberculosis challenge as a route to defining immune correlates of disease status or outcome.
确定可预测结核病疾病转归的免疫相关因素仍然是一项持续存在的挑战。为解决这一问题，我们评估了活动性结核病患者（ATBD，n = 10）、潜伏性结核感染患者（LTBI，n = 10）和既往活动性结核病患者（成功治疗后；PTBD，n = 10）外周血单个核细胞在体外受到结核分枝杆菌攻击后的基因表达谱，并与对照组（n = 10）进行比较。通过抑制性消减杂交、斑点印迹、实时聚合酶链反应和比较循环阈值方法评估差异基因表达谱。将ATBD样本与对照样本进行比较，发现多种趋化因子（CXCL1、CXCL3、IL8、MCP1、MIP1α）的基因表达增加倍数更大。与对照组相比，ATBD还与更高的IL1B基因表达相关。在LTBI样本中，与PTBD个体相比，几种趋化因子（CXCL2、CXCL3、IL8）的基因表达同样升高。我们的结果表明，ATBD和LTBI参与者的样本在体外受到结核分枝杆菌感染时具有不同的基因表达谱。这些发现表明，进一步表征外周对结核分枝杆菌攻击的反应，对于确定疾病状态或转归的免疫相关因素具有重要价值。
