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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-25

AUTHORS

Amy T Y Yeung, Christine Hale, Amy H Lee, Erin E Gill, Wendy Bushell, David Parry-Smith, David Goulding, Derek Pickard, Theodoros Roumeliotis, Jyoti Choudhary, Nick Thomson, William C Skarnes, Gordon Dougan, Robert E W Hancock

ABSTRACT

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. More... »

PAGES

15013

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms15013

DOI

http://dx.doi.org/10.1038/ncomms15013

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1085056188

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28440293


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