Aryl hydrocarbon receptor activation reduces dendritic cell function during influenza virus infection.
It has long been known that activation of the aryl hydrocarbon receptor (AhR) by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses T cell-dependent immune responses; however, the underlying cellular targets and mechanism remain unclear. We have previously shown that AhR activation by TCDD reduces the proliferation and differentiation of influenza virus-specific CD8(+) T cells through an indirect mechanism; suggesting that accessory cells are critical AhR targets during infection. Respiratory dendritic cells (DCs) capture antigen, migrate to lymph nodes, and play a key role in activating naive CD8(+) T cells during respiratory virus infection. Herein, we report an examination of how AhR activation alters DCs in the lung and affects their trafficking to and function in the mediastinal lymph nodes (MLN) during infection with influenza virus. We show that AhR activation impairs lung DC migration and reduces the ability of DCs isolated from the MLN to activate naive CD8(+) T cells. Using novel AhR mutant mice, in which the AhR protein lacks its DNA-binding domain, we show that the suppressive effects of TCDD require that the activated AhR complex binds to DNA. These new findings suggest that AhR activation by chemicals from our environment impacts DC function to stimulate naive CD8(+) T cells and that immunoregulatory genes within DCs are critical targets of AhR. Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection.
Jin
Guang-Bi
GB
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Moore
Amanda J
AJ
Head
Jennifer L
JL
Neumiller
Joshua J
JJ
Lawrence
B Paige
BP
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon