Emmanuel Enoch Dzakah1,2, Liping Huang3, Yaohua Xue1, Shuai Wei4, Xiaolin Wang4, Hongliang Chen5, Jingwei Shui3, Foster Kyei2, Farooq Rashid1, Heping Zheng1, Bing Yang1, Shixing Tang6,7. 1. Dermatology Hospital of Southern Medical University, Guangzhou, China. 2. Department of Molecular Biology and Biotechnology, School of Biological Sciences, College of Agriculture and Natural Sciences, University of Cape Coast, Cape Coast, Ghana. 3. Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. 4. 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, Hefei, China. 5. The First People's Hospital of Chenzhou, University of South China, Chenzhou, Hunan, China. 6. Dermatology Hospital of Southern Medical University, Guangzhou, China. tamgshixing@smu.edu.cn. 7. Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China. tamgshixing@smu.edu.cn.
Abstract
BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. RESULTS: 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-infectedpatients as compared to sera from healthy controls and HIV-1-infectedpatients. 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. CONCLUSIONS: 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.
Authors: Paul Shannon; Andrew Markiel; Owen Ozier; Nitin S Baliga; Jonathan T Wang; Daniel Ramage; Nada Amin; Benno Schwikowski; Trey Ideker Journal: Genome Res Date: 2003-11 Impact factor: 9.043