| Title: |
Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis. |
| Authors: |
Yeung, ATY; Hale, C; Lee, AH; Gill, EE; Bushell, W; Parry-Smith, D; Goulding, D; Pickard, D; Roumeliotis, T; Choudhary, J; Thomson, N; Skarnes, WC; Dougan, G; Hancock, REW |
| Contributors: |
Roumeliotis, Theodoros; Choudhary, Jyoti |
| Publisher Information: |
NATURE PUBLISHING GROUP |
| Publication Year: |
2020 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
Hela Cells; Macrophages; Humans; Chlamydia trachomatis; Chlamydia Infections; Gene Expression Profiling; Proteomics; Cell Differentiation; Mutation; Adult; Interferon Regulatory Factors; Interleukin-10 Receptor alpha Subunit; Host-Pathogen Interactions; Gene Knockout Techniques; Induced Pluripotent Stem Cells; Healthy Volunteers; CRISPR-Cas Systems; Gene Editing |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Electronic; ?; application/pdf |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
Nature communications, 2017, 8 pp. 15013 - ?; https://repository.icr.ac.uk/handle/internal/4164 |
| DOI: |
10.1038/ncomms15013 |
| Availability: |
https://doi.org/10.1038/ncomms15013; https://repository.icr.ac.uk/handle/internal/4164 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.978FB97D |
| Database: |
BASE |