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Microorganisms 2019, 7(3), 63; https://doi.org/10.3390/microorganisms7030063

Mycobacterium smegmatis But Not Mycobacterium avium subsp. hominissuis Causes Increased Expression of the Long Non-Coding RNA MEG3 in THP-1-Derived Human Macrophages and Associated Decrease of TGF-β

1
Department of Veterinary Medicine, Institute of Veterinary Biochemistry, Freie Universität Berlin, 14163 Berlin, Germany
2
Microbiology, Bioorganic & Macromolecular Chemistry Research Unit, Faculté de Pharmacie, Université Libre de Bruxelles, 1050 Brussels, Belgium
*
Author to whom correspondence should be addressed.
Received: 30 January 2019 / Revised: 13 February 2019 / Accepted: 26 February 2019 / Published: 27 February 2019
(This article belongs to the Special Issue Virulence Studies of Pathogenic Mycobacteria of Humans and Animal)
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Abstract

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 Mycobacterium tuberculosis or M. avium 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 M. smegmatis but not with the facultatively pathogenic M. avium subsp. hominissuis 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 M. smegmatis-infected macrophages but not in M. avium subsp. hominissuis pointing to lncRNAs as novel mediators of host cell response during mycobacterial infections. View Full-Text
Keywords: mycobacteria; long non-coding RNAs; lncRNA; DNA methyltransferases; MEG3; TGF-β; DNMT1; DNMT3b mycobacteria; long non-coding RNAs; lncRNA; DNA methyltransferases; MEG3; TGF-β; DNMT1; DNMT3b
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Sharbati, S.; Ravon, F.; Einspanier, R.; zur Bruegge, J. Mycobacterium smegmatis But Not Mycobacterium avium subsp. hominissuis Causes Increased Expression of the Long Non-Coding RNA MEG3 in THP-1-Derived Human Macrophages and Associated Decrease of TGF-β. Microorganisms 2019, 7, 63.

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