Lithium Inhibits Growth of Intracellular Mycobacterium kansasii through Enhancement of Macrophage Apoptosis

Hosung Sohn; Kwangwook Kim; Kil-Soo Lee; Han-Gyu Choi; Kang-In Lee; A-Rum Shin; Jong-Seok Kim; Sung Jae Shin; Chang-Hwa Song; Jeong-Kyu Park; Hwa-Jung Kim

doi:10.1007/s12275-014-3469-6

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Lithium Inhibits Growth of Intracellular Mycobacterium kansasii through Enhancement of Macrophage Apoptosis: Hosung Sohn ¹, Kwangwook Kim ¹, Kil-Soo Lee ², Han-Gyu Choi ¹, Kang-In Lee ¹, A-Rum Shin ¹, Jong-Seok Kim ³, Sung Jae Shin ³, Chang-Hwa Song ¹, Jeong-Kyu Park ¹, Hwa-Jung Kim ¹; Journal of Microbiology 2014;52(4):299-306.
DOI: https://doi.org/10.1007/s12275-014-3469-6
Published online: February 17, 2014

¹Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea, ²Department of Bacterial Respiratory Infections, Center for Infectious Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul 363-951, Republic of Korea, ³Department of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-749, Republic of Koreaa¹Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea, ²Department of Bacterial Respiratory Infections, Center for Infectious Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Seoul 363-951, Republic of Korea, ³Department of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-749, Republic of Koreaa

Corresponding author: Hwa-Jung Kim , Tel: +82-42-580-8242,

Received: 5 September 2013 • Accepted: 14 October 2013

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Abstract

Mycobacterium kansasii (Mk) is an emerging pathogen that causes a pulmonary disease similar to tuberculosis. Macrophage apoptosis contributes to innate host defense against mycobacterial infection. Recent studies have suggested that lithium significantly enhances the cytotoxic activity of death stimuli in many cell types. We examined the effect of lithium on the viability of host cells and intracellular Mk in infected macrophages. Lithium treatment resulted in a substantial reduction in the viability of intracellular Mk in macrophages. Macrophage cell death was significantly enhanced after adding lithium to Mk-infected cells but not after adding to uninfected macrophages. Lithium-enhanced cell death was due to an apoptotic response, as evidenced by augmented DNA fragmentation and caspase activation. Reactive oxygen species were essential for lithium-induced apoptosis. Intracellular scavenging by N-acetylcysteine abrogated the lithiummediated decrease in intracellular Mk growth as well as apoptosis. These data suggest that lithium is associated with control of intracellular Mk growth through modulation of the apoptotic response in infected macrophages.

Keywords: apoptosis;lithium;macrophage;Mycobacterium kansasii;reactive oxygen species

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Lithium Inhibits Growth of Intracellular Mycobacterium kansasii through Enhancement of Macrophage Apoptosis

J. Microbiol. 2014;52(4):299-306. Published online February 17, 2014

DOI: https://doi.org/10.1007/s12275-014-3469-6

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