Format

Send to

Choose Destination
Sci Rep. 2015 Aug 3;5:12689. doi: 10.1038/srep12689.

Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles.

Author information

1
1] Graduate Program in Biochemistry, Microbiology, and Molecular Biology [2] Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802.
2
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802.
3
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331.
4
Department of Pharmacology, Penn State College of Medicine, Hershey, PA 17033, USA.

Abstract

Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon the immunological status of the gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at the mucosal interface. However, the identity of the ligand(s) responsible for such AHR-mediated activation within the gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction and ligand structure activity analyses together with in silico modeling of the AHR ligand binding domain to identify indole, a microbial tryptophan metabolite, as a human-AHR selective agonist. Human AHR, acting as a host indole receptor may exhibit a unique bimolecular (2:1) binding stoichiometry not observed with typical AHR ligands. Such bimolecular indole-mediated activation of the human AHR within the gastrointestinal tract may provide a foundation for inter-kingdom signaling between the enteric microflora and the immune system to promote commensalism within the gut.

PMID:
26235394
PMCID:
PMC4522678
DOI:
10.1038/srep12689
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center