Abstract
Increasing evidence suggests that lncRNA is important in innate immune responses. Recent study has demonstrated that lncRNA NEAT1 (which has two subtypes: NEAT1_1 and NEAT1_2) nuclear-enriched abundant transcript 1 (NEAT1) is essential in immune regulation, but the expression and clinical significance in tuberculosis are still unclear. In this work, we aimed to discuss the expression and clinical significance of NEAT1 in tuberculosis patients. Quantitative real-time polymerase chain reaction was performed to detect the expression of NEAT1 (both NEAT1_1 and NEAT1_2) in peripheral blood mononuclear cells (PBMCs) of patients with tuberculosis and healthy controls and analyze the association of NEAT1 with the development, progression, and outcome of tuberculosis. Then NEAT1 was silenced in THP-1 cells using siRNA. The expression of tumor necrosis factor- (TNF-) α and interleukin- (IL-) 6 was detected after Mycobacterium tuberculosis (Mtb) infection, and the change in bactericidal capacity against Mtb was assessed. We demonstrated that the relative expression of NEAT1 (both NEAT1_1 and NEAT1_2) in patients with tuberculosis was higher than that in the control. However, the expression of NEAT1 (both NEAT1_1 and NEAT1_2) in the new case and relapse groups had insignificant differences. The level of NEAT1 (both NEAT1_1 and NEAT1_2) in PBMCs declined gradually with treatment and was restored to the normal level. The expression of NEAT1 (both NEAT1_1 and NEAT1_2) in THP-1 cells increased markedly after Mtb infection. The levels of IL-6 but not TNF-α in Mtb-infected THP-1 cells declined after the NEAT1 (both NEAT1_1 and NEAT1_2) knockout. The survival of Mtb in NEAT1-knockout (both NEAT1_1 and NEAT1_2) THP-1 cells reached its peak 72 h after infection, taking 0 h after Mtb infection as the baseline data; the difference was statistically significant compared with the control. Thus, our results indicate that the expression of NEAT1 increased during Mtb infection, and it might be associated with the outcome of tuberculosis. The decreased expression of NEAT1 might weaken the clearance of intracellular Mtb by macrophages.
Highlights
Tuberculosis is a chronic infectious disease significantly affecting human health
The expression of nuclear-enriched abundant transcript 1 (NEAT1) in peripheral blood mononuclear cells (PBMCs) of 106 patients and 55 controls was detected by qRT-PCR
Patients were further divided into new a case group (n = 75) and a relapse case group (n = 31) according to the history of antituberculosis treatment
Summary
Tuberculosis is a chronic infectious disease significantly affecting human health. The treatment of tuberculosis has become even more difficult due to a continuous increase in the number of resistant strains, and the occurrence of extensively drug-resistant tuberculosis brings new challenges to antituberculosis treatment [1]. A longterm epidemiologic study has shown that, the prevalence of Mycobacterium tuberculosis (Mtb) infection is high, only 5%–10% of the infections would develop into active tuberculosis, and the immune system is implicated in the development and progression of this disease [2]. Mtb is an intracellular parasite that lives in macrophages after infecting humans. The human body mainly relies on cellular immunity to fight against tuberculosis. How Mtb escapes from immune surveillance is still unclear, and tuberculosis is difficult to control
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