RGD Reference Report - Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major. - Rat Genome Database

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Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major.

Authors: Ehrchen, J  Helming, L  Varga, G  Pasche, B  Loser, K  Gunzer, M  Sunderkotter, C  Sorg, C  Roth, J  Lengeling, A 
Citation: Ehrchen J, etal., FASEB J. 2007 Oct;21(12):3208-18. Epub 2007 Jun 5.
RGD ID: 8158083
Pubmed: PMID:17551101   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.06-7261com   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
leishmaniasis  ISOVdr (Mus musculus)8158083; 8158083 RGD 
leishmaniasis  IMP 8158083 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vdr  (vitamin D receptor)

Genes (Mus musculus)
Vdr  (vitamin D (1,25-dihydroxyvitamin D3) receptor)

Genes (Homo sapiens)
VDR  (vitamin D receptor)


Additional Information