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

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 mimicks the infection of human blood-derived macrophages. Transcriptomic and proteomic profiling of the macrophage response to chlamydial infection highlights the role of the type I interferon and interleukin 10-mediated responses. Using CRISPR/Cas9 technology, we generate biallelic knockout mutations in the host genes encoding IRF5 and IL-10RA in iPSCs, confirming 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human) Chlamydia Trachomatis

TISSUE(S): Cell Culture, Macrophage

DISEASE(S): Chlamydia Trachomatis Infectious Disease

SUBMITTER: James Wright  

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD005858 | Pride | 2018-02-14

REPOSITORIES: Pride