Vaccine Discovery Division, La Jolla Institute for Immunology, La Jolla, CA, USA.
The Jenner Institute, University of Oxford, Oxford, UK.
Tuberculosis (Edinb). 2021 Dec;131:102127. doi: 10.1016/j.tube.2021.102127. Epub 2021 Sep 14.
Although only a small fraction will ever develop the active form of tuberculosis (ATB) disease, chemoprophylaxis treatment in latent TB infected (LTBI) individuals is an effective strategy to control pathogen transmission. Characterizing immune responses in LTBI upon chemoprophylactic treatment is important to facilitate treatment monitoring, and thus improve TB control strategies. Here, we studied changes in the blood transcriptome in a cohort of 42 LTBI and 8 ATB participants who received anti-TB therapy. Based on the expression of previously published gene signatures of progression to ATB, we stratified the LTBI cohort in two groups and examined if individuals deemed to be at elevated risk of developing ATB before treatment (LTBI-Risk) differed from others (LTBI-Other). We found that LTBI-Risk and LTBI-Other groups were associated with two distinct transcriptomic treatment signatures, with the LTBI-Risk signature resembling that of treated ATB patients. Notably, overlapping genes between LTBI-Risk and ATB treatment signatures were associated with risk of progression to ATB and interferon (IFN) signaling, and were selectively downregulated upon treatment in the LTBI-Risk but not the LTBI-Other group. Our results suggest that transcriptomic reprogramming following treatment of LTBI is heterogeneous and can be used to distinguish LTBI-Risk individuals from the LTBI cohort at large.
尽管只有一小部分人会发展为活动性结核病（ATB）疾病，但在潜伏性结核感染（LTBI）个体中进行化学预防治疗是控制病原体传播的有效策略。在化学预防治疗中描述 LTBI 个体的免疫反应对于促进治疗监测非常重要，从而改善结核病控制策略。在这里，我们研究了接受抗结核治疗的 42 名 LTBI 和 8 名 ATB 参与者的血液转录组的变化。基于先前发表的关于进展为 ATB 的基因特征表达，我们将 LTBI 队列分为两组，并检查在治疗前被认为具有较高发展为 ATB 风险的个体（LTBI-Risk）是否与其他个体（LTBI-Other）不同。我们发现，LTBI-Risk 和 LTBI-Other 组与两个不同的转录组治疗特征相关，LTBI-Risk 特征类似于治疗后的 ATB 患者。值得注意的是，LTBI-Risk 和 ATB 治疗特征之间重叠的基因与进展为 ATB 和干扰素（IFN）信号相关，并且在 LTBI-Risk 组中选择性地下调，但在 LTBI-Other 组中则没有。我们的研究结果表明，LTBI 治疗后的转录组重编程是异质的，可以用于区分 LTBI-Risk 个体与 LTBI 队列中的其他个体。
