title: Mincle-mediated translational regulation is required for strong nitric oxide production and inflammation resolution.
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.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Wook-Bin
authors.initials: WB
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Won Young
authors.initials: WY
authors.lastname: Choi
authors.affiliation: Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Quanri
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Chul Han
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Un Yung
authors.initials: UY
authors.lastname: Choi
authors.affiliation: Department of Integrative Bioscience and Biotechnology, College of Life Sciences, Sejong University, Seoul 05006, Republic of Korea.
authors.forename: Jeongsil
authors.initials: J
authors.lastname: Kim-Ha
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.|Department of Integrated Omics for Biomedical Science, Graduate School, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003311:Cord Factors / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006099:Granuloma / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D041681:NIH 3T3 Cells; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D003311:Cord Factors; D016207:Cytokines; D037181:Lectins, C-Type; D008239:Lysine; D008565:Membrane Proteins; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D000097574:Eukaryotic Translation Initiation Factor 5A; C113583:Clecsf8 protein, mouse; C100028:hypusine