Aryl Hydrocarbon Receptor Activation during Influenza Virus Infection Unveils a Novel Pathway of IFN-γ Production by Phagocytic Cells

作者: Haley Neff-LaFord , Sabine Teske , Timothy P. Bushnell , B. Paige Lawrence

DOI: 10.4049/JIMMUNOL.179.1.247

关键词: Aryl hydrocarbon receptorBiologyHaematopoiesisBone marrowLungImmunologyInfluenza A virusCD3CD11cVirus

摘要: The contribution of environmental factors is important as we consider reasons that underlie differential susceptibility to influenza virus. Aryl hydrocarbon receptor (AhR) activation by the pollutant dioxin during virus infection decreases survival, which correlates with a 4-fold increase in pulmonary IFN-gamma levels. We report here majority IFN-gamma-producing cells lung are neutrophils and macrophages not lymphocytes, elevated associated increased inducible NO synthase (iNOS) Moreover, show even absence dioxin, elicits production B cells, gammadelta T CD11c(+) neutrophils, well CD3(+) NK1.1(+) lung. Bone marrow chimeric mice reveal AhR-mediated events external hemopoietic direct dioxin-enhanced production. also increases dependent upon iNOS, but iNOS epithelial driven AhR-dependent signals from bone marrow-derived cells. Thus, contains targets AhR regulation, likely influence novel iNOS-mediated mechanism controls phagocytic This suggests changes response parenchymal such regulatory pathways cued respond inappropriately infection. These findings imply may contribute other respiratory pathogens.

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