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DOI: 10.1055/s-0032-1315481
Prenatal Acintebacter lwoffii exposure leads to protection against experimentally induced asthma in mice by epigenetic mechanisms
Background: During the last years several studies have revealed that exposure to a traditional farming environment during early live or already during pregnancy can protect children against the development of allergic disease like asthma. The reduced asthma susceptibility of these children might be mediated by epigenetic changes in immune cells induced by environmental triggers like exposure to microorganisms.
Method: In order to show that epigenetic changes can modulate the asthmatic phenotype we took advantage of a mouse model of experimental asthma. Pregnant mother mice were treated with the farm derived bacterium Acinetobacter lwoffii F78 and changes in histone acetylation and methylation at the IFNγ locus and the Th2 cytokine locus were analysed in CD4+ T cells.
Results: Treatment of pregnant mice with A. lwoffii leads to asthma protection in the offspring and increased IFNγ production. Blocking of IFNγ function with a neutralizing anti-IFNγ antibody interferes with protective effect in the progeny.
Histone acetylation is significantly increased at the IFNγ locus in CD4+ cells. Inhibition of histone acetlytion with the histone acetylase inhibitor Garcinol abolishes the protective effect in the progeny.
Conclusions: Prenatal exposure to the farm derived microbe A. lwoffii is able to induces asthma protection in the offspring of treated mice by the induction of IFNγ production. This effect is most likely mediated by an increased histone acetylation at the IFNγ locus.