Tuberculosis (TB) induced by Mycobacterium tuberculosis (M. tuberculosis) infection remains a global most deadly infectious disease. While development of more effective TB vaccines and therapeutics relies on identifications of true biomarkers designating an immune protection against M. tuberculosis infection, exact protective immune components against M. tuberculosis infection remain largely unidentified. We previously found that severe TB induced remarkable up-regulation of interferon regulatory factor 7 (IRF7) and IRF7-related gene signatures, implicating that some unknown downstream molecules in IRF7 signaling cascades may determine the M. tuberculosis infection outcomes and serve as a protective immune component against M. tuberculosis infection. Indeed, here, we observe that genetic ablation of IRF7 leads to more severe lung pathology, increased M. tuberculosis burdens, impaired differentiation of effector/memory T subsets, and extensively elevated expression of pro-inflammatory cytokines in lungs. Importantly, IRF7 is vital for sustaining expression of PD-1/PD-L1 and PD-1/PD-L1-modulated miRNA-31. Moreover, interventions of miRNA-31 expressions via administration of miRNA-31 agomir reduces lung pathology and bacilli burdens via inducing up-regulation of gene sets involved in biological processes of defense response or cellular and chemical homeostasis in lungs. Thus, this study uncovers previously unrecognized importance and mechanisms of IRF7-mediated miRNA-31 as a protective immune component against M. tuberculosis infection.

由结核分枝杆菌（M. tuberculosis ）感染引起的结核病（TB）仍然是全球最致命的传染病。虽然更有效的结核病疫苗和治疗方法的开发依赖于识别真正的生物标志物，这些生物标志物指定针对结核分枝杆菌感染的免疫保护，但针对结核分枝杆菌感染的确切保护性免疫成分仍然很大程度上尚未确定。我们之前发现，严重的结核病引起干扰素调节因子7（IRF7）和IRF7相关基因特征的显着上调，这意味着IRF7信号级联中的一些未知下游分子可能决定结核分枝杆菌感染的结果并充当保护性免疫抗结核分枝杆菌感染的成分。事实上，在这里，我们观察到 IRF7 的基因消融会导致更严重的肺部病理学、结核分枝杆菌负担增加、效应/记忆 T 亚群分化受损以及肺部促炎细胞因子表达广泛升高。重要的是，IRF7 对于维持 PD-1/PD-L1 和 PD-1/PD-L1 调节的 miRNA-31 的表达至关重要。此外，通过给予 miRNA-31 agomir 干预 miRNA-31 表达，可诱导参与肺部防御反应或细胞和化学稳态的生物过程的基因组上调，从而减少肺部病理学和杆菌负担。因此，这项研究揭示了 IRF7 介导的 miRNA-31 作为对抗结核分枝杆菌感染的保护性免疫成分的重要性和机制，这一点之前未被认识到。