Differential consequences of two distinct AhR ligands on innate and adaptive immune responses to influenza A virus.

Immune modulation by the aryl hydrocarbon receptor (AhR) has been primarily studied using 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). Recent reports suggest another AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ), exhibits distinct immunomodulatory properties, but side-by-side comparisons of these 2 structurally distinct, high-affinity ligands are limited. In this study, the effects of in vivo AhR activation with TCDD and FICZ were directly compared in a mouse model of influenza virus infection using 3 key measures of the host response to infection: pulmonary neutrophilia, inducible nitric oxide synthase (iNOS) levels, and the virus-specific CD8(+) T-cell response.

Novel cellular targets of AhR underlie alterations in neutrophilic inflammation and inducible nitric oxide synthase expression during influenza virus infection.

The underlying reasons for variable clinical outcomes from respiratory viral infections remain uncertain. Several studies suggest that environmental factors contribute to this variation, but limited knowledge of cellular and molecular targets of these agents hampers our ability to quantify or modify their contribution to disease and improve public health. The aryl hydrocarbon receptor (AhR) is an environment-sensing transcription factor that binds many anthropogenic and natural chemicals.