Host cell response and distinct gene expression profiles at different stages of Chlamydia trachomatis infection reveals stage-specific biomarkers of infection

BMC Microbiology

article

Dzakah, Emmanuel Enoch¹  Zheng, Heping¹  Yang, Bing¹  Tang, Shixing¹  Huang, Liping³  Xue, Yaohua¹  Wei, Shuai⁴  Wang, Xiaolin⁴  Chen, Hongliang⁵  Shui, Jingwei³  Kyei, Foster²  Rashid, Farooq¹ 

[1] Dermatology Hospital of Southern Medical University;Department of Molecular Biology and Biotechnology, School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast;Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University;Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China;The First People’s Hospital of Chenzhou, University of South China

关键词: Chlamydia trachomatis;    Differentially expressed genes;    Biomarkers;    Signaling pathways;    Replication;   

DOI  :  10.1186/s12866-020-02061-6

学科分类：放射科、核医学、医学影像

来源: BioMed Central

【 摘 要 】

Chlamydia trachomatis is the most common sexually transmitted infection and the bacterial agent of trachoma globally. C. trachomatis undergoes a biphasic developmental cycle involving an infectious elementary body and a replicative reticulate body. Little is currently known about the gene expression dynamics of host cell mRNAs, lncRNAs, and miRNAs at different stages of C. trachomatis development. Here, we performed RNA-seq and miR-seq on HeLa cells infected with C. trachomatis serovar E at 20 h post-infection (hpi) and 44 hpi with or without IFN-γ treatment. Our study identified and validated differentially expressed host cell mRNAs, lncRNAs, and miRNAs during infection. Host cells at 20 hpi showed the most differential upregulation of both coding and non-coding genes while at 44 hpi in the presence of IFN-γ resulted in a dramatic downregulation of a large proportion of host genes. Using RT-qPCR, we validated the top 5 upregulated mRNAs and miRNAs, which are specific for different stages of C. trachomatis development. One of the commonly expressed miRNAs at all three stages of C. trachomatis development, miR-193b-5p, showed significant expression in clinical serum samples of C. trachomatis-infected patients as compared to sera from healthy controls and HIV-1-infected patients. Furthermore, we observed significant upregulation of antigen processing and presentation, and T helper cell differentiation pathways at 20 hpi whereas T cell receptor, mTOR, and Rap1 pathways were modulated at 44 hpi. Treatment with IFN-γ at 44 hpi showed the upregulation of cytokine-cytokine receptor interaction, FoxO signaling, and Ras signaling pathways. Our study documented transcriptional manipulation of the host cell genomes and the upregulation of stage-specific signaling pathways necessary for the survival of the pathogen and could serve as potential biomarkers in the diagnosis and management of the disease.

【 授权许可】

CC BY|CC0