Project description:In a forward genetic screen we identified a Chlamydia trachomatis L2/434/Bu mutant that causes rapid apoptotic and necrotic death of infected host cells. This phenotype could be linked to the loss of the inclusion membrane protein CpoS. We observed a reduction in cell death when infections were carried out in the presence of cycloheximide or actinomycin D, suggesting that the engagement of cell death depends on host transcription and protein synthesis. We applied RNA-Seq to study the transcriptional response of human endocervical epithelial (A2EN) cells to infection with wild-type or CpoS-deficient bacteria. At 6 hpi the transcriptional profiles of cells infected with the two strains were similar to each other and to the transcriptome of uninfected cells. However, by 18 hpi the transcriptional profile of cells infected with the mutant was strongly altered, with 400 host genes being upregulated greater than two-fold. Among those differentially expressed genes, we observed an enrichment of immunity-related genes, including in particular cytokine genes and interferon-stimulated genes. Overall these data demonstrate that the CpoS-deficient mutant induces an exacerbated interferon response.
Project description:The aim of this study was to perform a microarray analysis of the response pattern of EEC from both large and small bowel to infection in vitro, using Chlamydia trachomatis infection as a model. Two human EEC lines: LCC-18, derived from a neuroendocrine colonic tumour, and CNDT-2, derived from a small intestinal carcinoid, were infected with C. trachomatis serovar LGV II strain 434 (ATCC VR-902B). Penicillin G was used to induce persistent infection. Gene expression levels in infected and persistently infected EEC cells were investigated by microarray analysis
