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Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis

Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach...

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Autores principales: Yeung, Amy T. Y., Hale, Christine, Lee, Amy H., Gill, Erin E., Bushell, Wendy, Parry-Smith, David, Goulding, David, Pickard, Derek, Roumeliotis, Theodoros, Choudhary, Jyoti, Thomson, Nick, Skarnes, William C., Dougan, Gordon, Hancock, Robert E. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414054/
https://www.ncbi.nlm.nih.gov/pubmed/28440293
http://dx.doi.org/10.1038/ncomms15013
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author Yeung, Amy T. Y.
Hale, Christine
Lee, Amy H.
Gill, Erin E.
Bushell, Wendy
Parry-Smith, David
Goulding, David
Pickard, Derek
Roumeliotis, Theodoros
Choudhary, Jyoti
Thomson, Nick
Skarnes, William C.
Dougan, Gordon
Hancock, Robert E. W.
author_facet Yeung, Amy T. Y.
Hale, Christine
Lee, Amy H.
Gill, Erin E.
Bushell, Wendy
Parry-Smith, David
Goulding, David
Pickard, Derek
Roumeliotis, Theodoros
Choudhary, Jyoti
Thomson, Nick
Skarnes, William C.
Dougan, Gordon
Hancock, Robert E. W.
author_sort Yeung, Amy T. Y.
collection PubMed
description Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlighted the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generated biallelic knockout mutations in host genes encoding IRF5 and IL-10RA in iPSCs, and confirmed their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections.
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spelling pubmed-54140542017-05-17 Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis Yeung, Amy T. Y. Hale, Christine Lee, Amy H. Gill, Erin E. Bushell, Wendy Parry-Smith, David Goulding, David Pickard, Derek Roumeliotis, Theodoros Choudhary, Jyoti Thomson, Nick Skarnes, William C. Dougan, Gordon Hancock, Robert E. W. Nat Commun Article Chlamydia trachomatis remains a leading cause of bacterial sexually transmitted infections and preventable blindness worldwide. There are, however, limited in vitro models to study the role of host genetics in the response of macrophages to this obligate human pathogen. Here, we describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. We show that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlighted the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generated biallelic knockout mutations in host genes encoding IRF5 and IL-10RA in iPSCs, and confirmed their roles in limiting chlamydial infection in macrophages. This model can potentially be extended to other pathogens and tissue systems to advance our understanding of host-pathogen interactions and the role of human genetics in influencing the outcome of infections. Nature Publishing Group 2017-04-25 /pmc/articles/PMC5414054/ /pubmed/28440293 http://dx.doi.org/10.1038/ncomms15013 Text en Copyright © 2017, The Author(s) 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
Yeung, Amy T. Y.
Hale, Christine
Lee, Amy H.
Gill, Erin E.
Bushell, Wendy
Parry-Smith, David
Goulding, David
Pickard, Derek
Roumeliotis, Theodoros
Choudhary, Jyoti
Thomson, Nick
Skarnes, William C.
Dougan, Gordon
Hancock, Robert E. W.
Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title_full Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title_fullStr Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title_full_unstemmed Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title_short Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis
title_sort exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing chlamydia trachomatis pathogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414054/
https://www.ncbi.nlm.nih.gov/pubmed/28440293
http://dx.doi.org/10.1038/ncomms15013
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