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.
Bibliographical noteFunding Information:
We thank S.J. Lee, J.E. See and H.R. Cho for caring for the mice and for excellent technical assistance. This research was supported by the Global Research Laboratory Program of the National Research Foundation (NRF), funded by the Ministry of Science, ICT and Future Planning (grant number: NRF-2007-00013 to Y.-J.K.); the Bio and Medical Technology Development Program of the NRF, funded by the Ministry of Science, ICT and Future Planning (grant number: NRF-2012M3A9B4028272 to Y.-J.K.).
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)