International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 206 - THE VITAMIN D RECEPTOR GENE AS AN INFECTION SUSCEPTIBILITY GENE: ANALYSIS OF IMMUNE MECHANISMS IN VDR-KO MICE

Helming L
Research Group Infection Genetics, GBF - German Research Center for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig

Co-Authors: 2) Ehrchen J, 3) Buer J, 3) Probst-Kepper M, 4) Gunzer M, 5) Erben R, 6) Balling R, 1) Lengeling A
Institutions: 2) Institute for Experimental Dermatology, University of Muenster, Roentgenstrasse 21, 48149 Muenster, 3) Research Group Mucosal Immunity, GBF - German Research Center for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig, 4) Research Group Immunodynamics, GBF - German Research Center for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig, 5) Institute of Animal Physiology, Ludwig Maximilians University, 80539 Munich, 6) GBF - German Research Center for Biotechnology, Mascheroder Weg 1, 38124 Braunschweig

Host genetic factors have profound influence on infection susceptibility to various pathogens. Polymorphisms and mutations in candidate genes have been associated with different outcome of several human infectious diseases. One of these candidate genes, which is being discussed as a putative infection susceptibility gene is the receptor for Vitamin D3 (VDR).

We used Vdr-knockout mice to analyse the role of the Vdr gene in susceptibility to infection. The preferred experimental model to study host defense to intracellular bacteria is infection with Listeria monocytogenes. We found that Vdr-Knockout mice are more susceptible to infection with Listeria. This is reflected by decreased survival of Vdr-KO mice and a more than ten-fold increase of viable Listeria in the livers but not in the spleens of Vdr-KO mice as compared to control animals.

In a second infection model we investigated the resistance of Vdr-knockout mice to the intracellular parasite Leishmania major. Again, we observed reduced resistance of Vdr-KO mice against this pathogen as compared to wildtype mice.

To elucidate the cellular mechanisms behind this impaired host responses, we immunized Vdr-KO mice with the defined antigen ovalbumin. In this vaccination model Vdr-KO mice exhibited a reduced T helper cell 1 (Th1) response.

Currently we are investigating if loss of VDR function might lead to abnormalities in innate immune mechanisms, especially regarding the macrophage and neutrophil response. This could lead alone or in combination with impaired T cell immunity to increased susceptibility of Vdr-knockout mice to intracellular pathogens. An update of this work will be presented.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012