PMID- 17551101
OWN - NLM
STAT- MEDLINE
DCOM- 20080107
LR  - 20131121
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 21
IP  - 12
DP  - 2007 Oct
TI  - Vitamin D receptor signaling contributes to susceptibility to infection with 
      Leishmania major.
PG  - 3208-18
AB  - 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.
FAU - Ehrchen, Jan
AU  - Ehrchen J
AD  - Institute for Experimental Dermatology, University of Munster, Munster, Germany.
FAU - Helming, Laura
AU  - Helming L
FAU - Varga, Georg
AU  - Varga G
FAU - Pasche, Bastian
AU  - Pasche B
FAU - Loser, Karin
AU  - Loser K
FAU - Gunzer, Matthias
AU  - Gunzer M
FAU - Sunderkotter, Cord
AU  - Sunderkotter C
FAU - Sorg, Clemens
AU  - Sorg C
FAU - Roth, Johannes
AU  - Roth J
FAU - Lengeling, Andreas
AU  - Lengeling A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070605
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Cytokines)
RN  - 0 (Receptors, Calcitriol)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 3.5.3.1 (Arginase)
RN  - FXC9231JVH (Calcitriol)
SB  - IM
MH  - Animals
MH  - Arginase/metabolism
MH  - Calcitriol/metabolism
MH  - Cytokines/immunology
MH  - Disease Susceptibility
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Leishmania major/*immunology/pathogenicity
MH  - Leishmaniasis, Cutaneous/*immunology
MH  - Macrophages/cytology/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
MH  - Phagocytosis
MH  - Receptors, Calcitriol/genetics/*metabolism
MH  - Signal Transduction/*physiology
MH  - T-Lymphocytes/metabolism
EDAT- 2007/06/07 09:00
MHDA- 2008/01/08 09:00
CRDT- 2007/06/07 09:00
PHST- 2007/06/07 09:00 [pubmed]
PHST- 2008/01/08 09:00 [medline]
PHST- 2007/06/07 09:00 [entrez]
AID - fj.06-7261com [pii]
AID - 10.1096/fj.06-7261com [doi]
PST - ppublish
SO  - FASEB J. 2007 Oct;21(12):3208-18. doi: 10.1096/fj.06-7261com. Epub 2007 Jun 5.