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Publication : The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma.

First Author  Smit JJ Year  2003
Journal  J Immunol Volume  171
Issue  2 Pages  754-60
PubMed ID  12847242 Mgi Jnum  J:84289
Mgi Id  MGI:2667277 Doi  10.4049/jimmunol.171.2.754
Citation  Smit JJ, et al. (2003) The Slc11a1 (Nramp1) gene controls efficacy of mycobacterial treatment of allergic asthma. J Immunol 171(2):754-60
abstractText  Genes controlling antibacterial resistance may be important in the hygiene hypothesis, which states that lack of bacterial infections during childhood would favor development of allergic disease. We, therefore, studied whether Nramp1 (Slc11a1) alleles, which determine susceptibility (Nramp1(s)) or resistance (Nramp1(r)) to intracellular bacteria, affect the efficacy of heat-killed Mycobacterium vaccae in the treatment of allergic asthma in a mouse model. Treatment of OVA-sensitized Nramp1(s) mice with M. vaccae suppressed airway hyperresponsiveness, airway eosinophilia, Ag-specific IgE, and IL-4 and IL-5 production after OVA aerosol challenge. In contrast, M. vaccae hardly affected these parameters in Nramp1(r) mice. In addition, The Nramp1 gene affected both T cell-mediated responses to M. vaccae in vivo and the level of macrophage activation after stimulation with M. vaccae in vitro. In conclusion, the efficacy of M. vaccae in preventing allergic and asthmatic manifestations in a mouse model is strongly affected by Nramp1 alleles. These findings could have important implications for the future use of mycobacteria and their components in the prevention or treatment of allergic asthma. A new link is described between genes, the environment, and the development of allergy, in which the Nramp1 gene fine tunes the hygiene hypothesis.
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