Taneja Vibha, Kalra Priya, Goel Manish, Khilnani Gopi Chand, Saini Vikram, Prasad G B K S, Gupta Umesh Datta, Krishna Prasad Hanumanthappa
National JALMA Institute of Leprosy and Other Mycobacterial Diseases, Tajganj, Agra, India.
Department of Biochemistry, Jiwaji University, Gwalior, Madhya Pradesh, India.
PLoS One. 2020 Jul 15;15(7):e0235488. doi: 10.1371/journal.pone.0235488. eCollection 2020.
Mycobacterium tuberculosis (M.tb) infection stimulates the release of cytokines, including interferons (IFNs). IFNs are initiators, regulators, and effectors of innate and adaptive immunity. Accordingly, the expression levels of Type I (α, β) and II (γ) IFNs, among untreated tuberculosis (TB) patients and household contacts (HHC) clinically free of TB was assessed. A total of 264 individuals (TB patients-123; HHC-86; laboratory volunteers-55; Treated TB patients-36) were enrolled for this study. IFN-α mRNA expression levels predominated compared to IFN-γ and IFN-β among untreated TB patients. IFN-α transcripts were ~3.5 folds higher in TB patients compared to HHC, (p<0.0001). High expression of IFN-α was seen among 46% (56/ 123) of the TB patients and 26%, (22/86) of HHCs. The expression levels of IFN-α correlated with that of IFN transcriptional release factor 7 (IRF) (p<0.0001). In contrast, an inverse relationship exists between PGE2 and IFN-α expression levels; high IFN-α expressers were associated with low levels of PGE2 and vice-versa (Spearman's rho = -0.563; p<0.0001). In-vitro, IFN-α failed to restrict the replication of intracellular M.tb. The anti-mycobacterial activity of IFN-γ was compromised in the presence of IFN-α, but not by IFN-β. The expression of IFN-α and β diminished or is absent, among successfully treated TB patients. These observations suggest the utility of assessment of Type I IFNs expression levels as a prognostic marker to monitor tuberculosis patient response to chemotherapy because changes in Type I IFNs expression are expected to precede the clearance and /reduction in bacterial load.
结核分枝杆菌（M.tb）感染会刺激细胞因子的释放，包括干扰素（IFN）。IFN是先天性和适应性免疫的启动子、调节因子和效应器。因此，我们评估了未经治疗的结核病（TB）患者和临床上无结核病的家庭接触者（HHC）中I型（α、β）和II型（γ）IFN的表达水平。本研究共纳入264名个体（TB患者123名；HHC 86名；实验室志愿者55名；接受治疗的TB患者36名）。在未经治疗的TB患者中，IFN-α mRNA表达水平高于IFN-γ和IFN-β。与HHC相比，TB患者的IFN-α转录本高约3.5倍（p<0.0001）。46%（56/123）的TB患者和26%（22/86）的HHC中可见IFN-α高表达。IFN-α的表达水平与IFN转录释放因子7（IRF）的表达水平相关（p<0.0001）。相反，PGE2与IFN-α表达水平呈负相关；IFN-α高表达者与低水平的PGE2相关，反之亦然（斯皮尔曼等级相关系数=-0.563；p<0.0001）。在体外，IFN-α无法限制细胞内M.tb的复制。在存在IFN-α的情况下，IFN-γ的抗分枝杆菌活性受到损害，但不受IFN-β的影响。在成功治疗的TB患者中，IFN-α和β的表达减少或不存在。这些观察结果表明，评估I型IFN表达水平作为一种预后标志物来监测结核病患者对化疗的反应具有实用性，因为I型IFN表达的变化预计会先于细菌载量的清除和/减少。
