A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis

Fei-yu Wang; Yu-qing Zhang; Xin-min Wang; Chan Wang; Xiao-fang Wang; Jiang-dong Wu; Fang Wu; Wan-jiang Zhang; Le Zhang

doi:10.1007/s12275-016-5627-5

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Research Support, Non-U.S. Gov't
A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis: Fei-yu Wang ^1,2, Yu-qing Zhang ^1,2, Xin-min Wang ^2,3, Chan Wang ^2,4, Xiao-fang Wang ^1,2, Jiang-dong Wu ^1,2, Fang Wu ^1,2, Wan-jiang Zhang ^1,2, Le Zhang ^1,2; Journal of Microbiology 2016;54(4):330-337.
DOI: https://doi.org/10.1007/s12275-016-5627-5
Published online: April 1, 2016

¹Department of Pathophysiology, Medical College of Shihezi University, Xinjiang, P. R. China, ²Key Laboratory of Xinjiang Endemic and Ethnic Diseases Cooperated by Education Ministry with Xinjiang Province, Xinjiang, Shihezi, P. R. China, ³Department of Urinary Surgery, the First Affiliated Hospital, Xinjiang, Shihezi, P. R. China, ⁴Department of Pathogen Biology and Immunology, Medical College of Shihezi University, Xinjiang, P. R. China¹Department of Pathophysiology, Medical College of Shihezi University, Xinjiang, P. R. China, ²Key Laboratory of Xinjiang Endemic and Ethnic Diseases Cooperated by Education Ministry with Xinjiang Province, Xinjiang, Shihezi, P. R. China, ³Department of Urinary Surgery, the First Affiliated Hospital, Xinjiang, Shihezi, P. R. China, ⁴Department of Pathogen Biology and Immunology, Medical College of Shihezi University, Xinjiang, P. R. China

Corresponding author: Le Zhang , Tel: +86-0993-20-57151,

Received: 21 December 2015 • Revised: 19 February 2016 • Accepted: 22 February 2016

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Abstract

Myeloid cell leukemia-1 (Mcl-1) plays an important role in various cell survival pathways. Some studies indicated that the expression of Mcl-1 was upregulated in host cells during infection with the virulent Mycobacterium tuberculosis strain, H37Rv. The present study was designed to investigate the effect of inhibiting Mcl-1 expression both in vivo and in vitro on apoptosis of host macrophages infected with M. tuberculosis using a small hairpin (sh)RNA. Mcl-1 expression was detected by the real time-polymerase chain reaction, western blotting, and immunohistochemistry. Flow cytometry and transmission electron microscopy were used to measure host macrophage apoptosis. We found elevated Mcl-1 levels in host macrophages infected with M. tuberculosis H37Rv. The expression of Mcl-1 was downregulated efficiently in H37Rv-infected host macrophages using shRNA. Knockdown of Mcl-1 enhanced the extent of apoptosis in H37Rv-infected host macrophages significantly. The increased apoptosis correlated with a decrease in M. tuberculosis colony forming units recovered from H37Rv-infected cells that were treated with Mcl-1-shRNA. Reducing Mcl-1 accumulation by shRNA also reduced accumulation of the anti-apoptotic gene, Bcl-2, and increased expression of the pro-apoptotic gene, Bax, in H37Rv-infected host macrophages. Our results showed that specific knockdown of Mcl-1 expression increased apoptosis of host macrophages significantly and decreased the intracellular survival of a virulent strain of M. tuberculosis. These data indicate that interference with Mcl-1 expression may provide a new avenue for tuberculosis therapy.

Keywords: apoptosis;Mcl-1;Mcl-1-shRNA;Mycobacterium tuberculosis;host macrophages

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A small hairpin RNA targeting myeloid cell leukemia-1 enhances apoptosis in host macrophages infected with Mycobacterium tuberculosis

J. Microbiol. 2016;54(4):330-337. Published online April 1, 2016

DOI: https://doi.org/10.1007/s12275-016-5627-5

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