دورية أكاديمية
Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis.
| العنوان: | Exploiting induced pluripotent stem cell-derived macrophages to unravel host factors influencing Chlamydia trachomatis pathogenesis. |
|---|---|
| المؤلفون: | Yeung ATY; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Hale C; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Lee AH; Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4., Gill EE; Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4., Bushell W; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Parry-Smith D; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Goulding D; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Pickard D; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Roumeliotis T; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Choudhary J; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Thomson N; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Skarnes WC; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK., Dougan G; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.; Department of Medicine, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK., Hancock REW; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK.; Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4. |
| المصدر: | Nature communications [Nat Commun] 2017 Apr 25; Vol. 8, pp. 15013. Date of Electronic Publication: 2017 Apr 25. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [London] : Nature Pub. Group |
| مواضيع طبية MeSH: | Chlamydia Infections/*genetics , Chlamydia trachomatis/*pathogenicity , Host-Pathogen Interactions/*genetics , Macrophages/*physiology, Adult ; CRISPR-Cas Systems/genetics ; Cell Differentiation ; Chlamydia Infections/immunology ; Chlamydia Infections/microbiology ; Chlamydia trachomatis/immunology ; Gene Editing/methods ; Gene Expression Profiling ; Gene Knockout Techniques ; HeLa Cells ; Healthy Volunteers ; Host-Pathogen Interactions/immunology ; Humans ; Induced Pluripotent Stem Cells/physiology ; Interferon Regulatory Factors/genetics ; Interferon Regulatory Factors/immunology ; Interleukin-10 Receptor alpha Subunit/genetics ; Interleukin-10 Receptor alpha Subunit/immunology ; Macrophages/microbiology ; Mutation ; Proteomics/methods |
| مستخلص: | 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. |
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| معلومات مُعتمدة: | United Kingdom Wellcome Trust |
| المشرفين على المادة: | 0 (IRF5 protein, human) 0 (Interferon Regulatory Factors) 0 (Interleukin-10 Receptor alpha Subunit) |
| تواريخ الأحداث: | Date Created: 20170426 Date Completed: 20181120 Latest Revision: 20181120 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5414054 |
| DOI: | 10.1038/ncomms15013 |
| PMID: | 28440293 |
| قاعدة البيانات: | MEDLINE |
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