Cargando…
Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles
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 fo...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522678/ https://www.ncbi.nlm.nih.gov/pubmed/26235394 http://dx.doi.org/10.1038/srep12689 |
_version_ | 1782383993112494080 |
---|---|
author | Hubbard, Troy D. Murray, Iain A. Bisson, William H. Lahoti, Tejas S. Gowda, Krishne Amin, Shantu G. Patterson, Andrew D. Perdew, Gary H. |
author_facet | Hubbard, Troy D. Murray, Iain A. Bisson, William H. Lahoti, Tejas S. Gowda, Krishne Amin, Shantu G. Patterson, Andrew D. Perdew, Gary H. |
author_sort | Hubbard, Troy D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4522678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45226782015-08-06 Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles Hubbard, Troy D. Murray, Iain A. Bisson, William H. Lahoti, Tejas S. Gowda, Krishne Amin, Shantu G. Patterson, Andrew D. Perdew, Gary H. Sci Rep Article 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. Nature Publishing Group 2015-08-03 /pmc/articles/PMC4522678/ /pubmed/26235394 http://dx.doi.org/10.1038/srep12689 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Hubbard, Troy D. Murray, Iain A. Bisson, William H. Lahoti, Tejas S. Gowda, Krishne Amin, Shantu G. Patterson, Andrew D. Perdew, Gary H. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title | Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title_full | Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title_fullStr | Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title_full_unstemmed | Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title_short | Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
title_sort | adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4522678/ https://www.ncbi.nlm.nih.gov/pubmed/26235394 http://dx.doi.org/10.1038/srep12689 |
work_keys_str_mv | AT hubbardtroyd adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT murrayiaina adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT bissonwilliamh adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT lahotitejass adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT gowdakrishne adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT aminshantug adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT pattersonandrewd adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles AT perdewgaryh adaptationofthehumanarylhydrocarbonreceptortosensemicrobiotaderivedindoles |