| First Author | Fritsche G | Year | 2008 |
| Journal | Eur J Immunol | Volume | 38 |
| Issue | 11 | Pages | 3060-7 |
| PubMed ID | 18991287 | Mgi Jnum | J:141403 |
| Mgi Id | MGI:3818217 | Doi | 10.1002/eji.200838449 |
| Citation | Fritsche G, et al. (2008) Nramp1-functionality increases iNOS expression via repression of IL-10 formation. Eur J Immunol 38(11):3060-7 |
| abstractText | In mice, resistance to certain intracellular microbes depends on the expression of a late phagosomal protein termed natural-resistance associated macrophage protein 1 (Nramp1, Slc11a1). Nramp1-functionality is associated with alterations of cellular iron homeostasis and a sustained pro-inflammatory immune response, including the formation of the antimicrobial effector molecule NO. To investigate the underlying mechanism we used RAW-264.7 murine macrophage cells stably transfected with a functional Nramp1 allele (RAW-37) or Nramp1 non-functional controls (RAW-21). We found that the production of and signalling by the anti-inflammatory cytokine IL-10 was significantly enhanced in macrophages lacking functional Nramp1. Upon infection of macrophages with Salmonella typhimurium pathogen survival was significantly better in RAW-21 than in RAW-37, which inversely correlated to NO and TNF-alpha formation. Addition of a neutralising anti-IL-10 antibody to RAW-21 cells led to a significantly reduced survival of S. typhimurium within these cells and enhanced formation of NO and TNF-alpha reaching levels comparable to that observed in cells bearing functional Nramp1. Oppositely, supplementation of iron to RAW-21 cells further increased IL-10 formation.Thus, Nramp1 mediates effective host defence in part via suppression of excessive IL-10 production which may relate to Nramp1-mediated reduction of cellular iron pools, thus strengthening antimicrobial effector mechanisms. |
