Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis.
Loading...
Embargo End Date
ICR Authors
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
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
Document Type
Journal Article
Date
2017-04-25
Date Accepted
2017-02-21
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.
Citation
Nature communications, 2017, 8 pp. 15013 - ?
Source Title
Publisher
NATURE PUBLISHING GROUP
ISSN
2041-1723
eISSN
2041-1723