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

作者：Hubbard, Troy D.; Murray, Iain A.; Bisson, William H.; Lahoti, Tejas S.; Gowda, Krishne; Amin, Shantu G.; Patterson, Andrew D.; Perdew, Gary H.^*

来源：Scientific Reports, 2015, 5(1): 12689.

DOI：10.1038/srep12689

• ESCHERICHIA-COLI
• TRYPTOPHAN-METABOLITES
• MALASSEZIA-FURFUR
• INHIBITS COLITIS
• LIGAND
• ACTIVATION
• CELLS
• AGONIST
• SIGNAL
• IDENTIFICATION

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.

• 出版日期2015-8-3