cord-factors and hypusine

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.

Topics: Animals; Cell Line; Cells, Cultured; Cord Factors; Cytokines; Eukaryotic Translation Initiation Factor 5A; Gene Expression; Granuloma; Immunoblotting; Inflammation; Lectins, C-Type; Lysine; Macrophages; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mycobacterium tuberculosis; NIH 3T3 Cells; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Peptide Initiation Factors; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA-Binding Proteins; Toll-Like Receptors