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There are, however, limited <jats:italic>in vitro<\/jats:italic> 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\u2013<jats:italic>Chlamydia<\/jats:italic> interactions <jats:italic>in vitro<\/jats:italic>. We show that iPSdMs support the full infectious life cycle of <jats:italic>C. trachomatis<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/ncomms15013","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T10:07:26Z","timestamp":1493114846000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis"],"prefix":"10.1038","volume":"8","author":[{"given":"Amy T. 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