Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution

Wook-Bin Lee, Ji-Seon Kang, Won Young Choi, Quanri Zhang, Chul Han Kim, Un Yung Choi, Jeongsil Kim-Ha and Young-Joon Kim ()
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Wook-Bin Lee: College of Life Science and Biotechnology, Yonsei University
Ji-Seon Kang: College of Life Science and Biotechnology, Yonsei University
Won Young Choi: Graduate School, Yonsei University
Quanri Zhang: Graduate School, Yonsei University
Chul Han Kim: Graduate School, Yonsei University
Un Yung Choi: College of Life Science and Biotechnology, Yonsei University
Jeongsil Kim-Ha: College of Life Sciences, Sejong University
Young-Joon Kim: College of Life Science and Biotechnology, Yonsei University

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract In response to persistent mycobacteria infection, the host induces a granuloma, which often fails to eradicate bacteria and results in tissue damage. Diverse host receptors are required to control the formation and resolution of granuloma, but little is known concerning their regulatory interactions. Here we show that Mincle, the inducible receptor for mycobacterial cord factor, is the key switch for the transition of macrophages from cytokine expression to high nitric oxide production. In addition to its stimulatory role on TLR-mediated transcription, Mincle enhanced the translation of key genes required for nitric oxide synthesis through p38 and eIF5A hypusination, leading to granuloma resolution. Thus, Mincle has dual functions in the promotion and subsequent resolution of inflammation during anti-mycobacterial defence using both transcriptional and translational controls.

Date: 2016
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DOI: 10.1038/ncomms11322

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