Sharbati Soroush, Ravon Faustine, Einspanier Ralf, Zur Bruegge Jennifer
Department of Veterinary Medicine, Institute of Veterinary Biochemistry, Freie Universität Berlin, 14163 Berlin, Germany.
Microbiology, Bioorganic & Macromolecular Chemistry Research Unit, Faculté de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium.
Microorganisms. 2019 Feb 27;7(3):63. doi: 10.3390/microorganisms7030063.
Pathogenic mycobacteria are able to persist intracellularly in macrophages, whereas non-pathogenic mycobacteria are effectively combated and eliminated after their phagocytosis. It is known that TGF-β plays an important role in this context. Infection with pathogenic mycobacteria such as or leads to production of active TGF-β, which blocks the ability of IFN-γ and TNF-α to inhibit intracellular replication. On the other hand, it is known that the long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) is involved in the regulation of TGF-β. In this study, we show how the infection of THP-1-derived human macrophages with the saprophytic but not with the facultatively pathogenic subsp. leads to increased MEG3 expression. This is associated with the downregulation of DNA methyltransferases (DNMT) 1 and 3b, which are known to regulate MEG3 expression via promoter hypermethylation. Consequently, we observe a significant downregulation of TGF-β in -infected macrophages but not in subsp. pointing to lncRNAs as novel mediators of host cell response during mycobacterial infections.
致病性分枝杆菌能够在巨噬细胞内持续存在，而非致病性分枝杆菌在被吞噬后会被有效对抗并清除。已知转化生长因子-β（TGF-β）在此过程中起重要作用。感染致病性分枝杆菌（如 或 ）会导致活性TGF-β的产生，它会阻断干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）抑制细胞内复制的能力。另一方面，已知长链非编码RNA（lncRNA）母源表达基因3（MEG3）参与TGF-β的调控。在本研究中，我们展示了腐生性 而非兼性致病性 亚种感染THP-1来源的人巨噬细胞如何导致MEG3表达增加。这与DNA甲基转移酶（DNMT）1和3b的下调有关，已知它们通过启动子高甲基化来调节MEG3的表达。因此，我们观察到在 感染的巨噬细胞中TGF-β显著下调，但在 亚种感染的巨噬细胞中未观察到，这表明lncRNAs是分枝杆菌感染期间宿主细胞反应的新型介质。
