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lüll The aryl hydrocarbon receptor is a modulator of anti-viral immunity Head JL; Lawrence BPBiochem Pharmacol 2009[Feb]; 77 (4): 642-53Although immune modulation by AhR ligands has been studied for many years, the impact of AhR activation on host defenses against viral infection has not, until recently, garnered much attention. The development of novel reagents and model systems, new information regarding anti-viral immunity, and a growing appreciation for the global health threat posed by viruses have invigorated interest in understanding how environmental signals affect susceptibility to and pathological consequences of viral infection. Using influenza A virus as a model of respiratory viral infection, recent studies show that AhR activation cues signaling events in both leukocytes and non-immune cells. Functional alterations include suppressed lymphocyte responses and increased inflammation in the infected lung. AhR-mediated events within and extrinsic to hematopoietic cells has been investigated using bone marrow chimeras, which show that AhR alters different elements of the immune response by affecting different tissue targets. In particular, suppressed CD8(+) T cell responses are due to deregulated events within leukocytes themselves, whereas increased neutrophil recruitment to and IFN-gamma levels in the lung result from AhR-regulated events extrinsic to bone marrow-derived cells. This latter discovery suggests that epithelial and endothelial cells are overlooked targets of AhR-mediated changes in immune function. Further support that AhR influences host cell responses to viral infection are provided by several studies demonstrating that AhR interacts directly with viral proteins and affects viral latency. While AhR clearly modulates host responses to viral infection, we still have much to understand about the complex interactions between immune cells, viruses, and the host environment.|Environmental Pollutants/toxicity[MESH]|Humans[MESH]|Immunity, Innate/drug effects/*physiology[MESH]|Immunologic Factors/immunology/physiology[MESH]|Influenza, Human/immunology/metabolism[MESH]|Polychlorinated Dibenzodioxins/toxicity[MESH]|Receptors, Aryl Hydrocarbon/metabolism/*physiology[MESH]|Virus Diseases/*immunology/metabolism[MESH] |