| First Author | Ehrchen J | Year | 2007 |
| Journal | FASEB J | Volume | 21 |
| Issue | 12 | Pages | 3208-18 |
| PubMed ID | 17551101 | Mgi Jnum | J:134827 |
| Mgi Id | MGI:3789858 | Doi | 10.1096/fj.06-7261com |
| Citation | Ehrchen J, et al. (2007) Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major. FASEB J 21(12):3208-18 |
| abstractText | We have previously reported that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) can selectively suppress key functions of interferon-gamma (IFN-gamma) activated macrophages. To further explore this mechanism for its relevance in vivo, we investigated an infection model that crucially depends on the function of IFN-gamma activated macrophages, the infection with the intracellular protozoan Leishmania major. 1Alpha,25(OH)2D3 treatment of L. major infected macrophages demonstrated a vitamin D receptor (Vdr) dependent inhibition of macrophage killing activity. Further analysis showed that this was a result of decreased production of nitric oxide by 1alpha,25(OH)2D3-treated macrophages due to Vdr-dependent up-regulation of arginase 1 expression, which overrides NO production by Nos2. When analyzing the course of infection in vivo, we found that Vdr-knockout (Vdr-KO) mice were more resistant to L. major infection than their wild-type littermates. This result is in agreement with an inhibitory influence of 1alpha,25(OH)2D3 on the macrophage mediated host defense. Further investigation showed that Vdr-KO mice developed an unaltered T helper cell type 1 (Th1) response on infection as indicated by normal production of IFN-gamma by CD4+ and CD8+ T cells. Therefore, we propose that the absence of 1alpha,25(OH)2D3-mediated inhibition of macrophage microbicidal activity in Vdr-KO mice results in increased resistance to Leishmania infection. |
