AUTHOR=Wang Jie , Hussain Tariq , Yue Ruichao , Liao Yi , Li Qiang , Yao Jiao , Song Yinjuan , Sun Xin , Wang Nan , Xu Lei , Sreevatsan Srinand , Zhao Deming , Zhou Xiangmei 

TITLE=MicroRNA-199a Inhibits Cellular Autophagy and Downregulates IFN-β Expression by Targeting TBK1 in Mycobacterium bovis Infected Cells

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00238

DOI=10.3389/fcimb.2018.00238

ISSN=2235-2988

ABSTRACT=<p>The mechanism by which microRNAs (miRNAs) modulate innate immunity and autophagy has not been fully elucidated in <italic>Mycobacterium bovis</italic> (<italic>M. bovis</italic>) infections. In this study, we identified that miR-199a inhibited key innate immune responses and autophagy in murine macrophages infected with <italic>M. bovis</italic>. Using <italic>ex vivo</italic> and <italic>in vitro</italic> approaches we show that the expression of miR-199a was significantly increased during <italic>M. bovis</italic> infection. Furthermore, miR-199a suppressed autophagy and interferon-β (IFN-β) production by directly targeting TANK-binding kinase 1 (TBK1) mRNA in both J774a.1 and BMDM cells. Upregulation of miR-199a or TBK1 silencing (siTBK1) inhibited maturation of autophagosomes and increased <italic>M. bovis</italic> survival. Our results demonstrate that, by targeting of TBK1, miR-199a modulates innate immune responses and promote the intracellular survival and growth of <italic>M. bovis</italic>.</p>