Therapeutic potential of nutritional aryl hydrocarbon receptor ligands for respiratory syncytial virus infection: a mini review.

Respiratory syncytial virus (RSV) infection is still a major cause of hospitalization of young children and older adults. Despite recent significant advances, critical gaps remain in prevention strategies, particularly for older infants and underserved populations, and to date there is no specific treatment available. The aryl hydrocarbon receptor (AHR) is a transcription factor initially identified as mediator of the toxic effects of environmental pollutants that was later found to be also activated by ligands derived from food, the gut microbiome, and host metabolism. AHR activation by these naturally occurring, or nutritional, ligands has been associated with beneficial physiological processes. Notably, AHR has critical functions in barrier organs such as the lungs, including regulation of immune responses to infection. AHR activation is a common strategy for many viruses to evade antiviral immunity, but in a recently published study we found that during RSV infection the AHR pathway is downregulated and plays a protective role, and the administration of the dietary AHR pro-ligand indole-3-carbinol (I3C) to RSV-infected mice led to beneficial effects. Here we review and discuss studies indicating nutritional AHR ligands, particularly compounds derived from cruciferous vegetables or generated during the metabolism of tryptophan, may offer therapeutic benefit for RSV disease, by positively modulating inflammation and reducing excessive immune responses, oxidative stress, and viral replication.