Project description:This SuperSeries is composed of the following subset Series: GSE6209: The global transcriptional profile of Mycobacterium tuberculosis during human macrophages infection GSE7962: Sigma factor E of Mycobacterium tuberculosis controls the expression of bacterial components that modulate macrophages Keywords: SuperSeries Refer to individual Series
Project description:This study investigates the proteomic alterations in human monocytic cell line (THP1) subsequent to infection with different strains of mycobacterium tuberculosis (H37Ra, H37Rv, BND433 and JAL2287) using the SWATH-MS strategy. THP1 proteome was analysed after 6, 18, 30 and 42 hours of infection with each strains and compared to that of uninfected cells. Our findings reveal temporal regulation of host response subsequent to Mtb infection.
Project description:This study investigates the proteomic alterations in human monocytic cell line (THP1) subsequent to infection with different strains of mycobacterium tuberculosis (H37Ra, H37Rv, BND433 and JAL2287) using the SWATH-MS strategy. THP1 proteome was analysed after 6, 18, 30 and 42 hours of infection with each strains and compared to that of uninfected cells. Our findings reveal temporal regulation of host response subsequent to Mtb infection.
Project description:Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs) causing pulmonary tuberculosis (PTB), the more frequent form of the disease. Less frequently, Mtb disseminates to many other organs and tissues resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, in particular from humans with the active form of the disease. Strikingly, almost no studies have addressed the response to infection with Mtb by human extrapulmonary macrophages.
Project description:Identification of genetic polymorphisms associated with inter-individual variation in immune response to Mycobacterium tuberculosis infection.
Project description:In order to investigate the impact of using in vitro techniques to generate single cell suspensions of Mycobacterium tuberculosis (Mtb) on macrophage gene expression, we compared uninfected bone marrow derived macrophages to macrophages infected with Mtb that was prepared using gentle sonication followed by low-speed centrifugation (so/sp) or passage through a 5 µm syringe filter (5µmF).
Project description:Mycobacterium tuberculosis (Mtb) is well adapted to survive in macrophages and usually subverts the bactericidal mechanisms of these professional phagocytes. The adaptation of Mtb to the intracellular life depends on its ability to regulate the expression of its genes. Among the most important bacterial transcription activators are the sigma factors that bind to the RNA polymerase and give it promotor specificity. Sigma factor E (SigE) controls the expression of genes that are essential for Mtb virulence. Analysis of the macrophage transcriptional response indicated that proteins encoded by the sigE regulon are involved in the modulation of the macrophage inflammatory response. Keywords: Comparison of responses to infections
Project description:Mycobacterium tuberculosis (Mtb) is well adapted to survive in macrophages and usually subverts the bactericidal mechanisms of these professional phagocytes. The adaptation of Mtb to the intracellular life depends on its ability to regulate the expression of its genes. Among the most important bacterial transcription activators are the sigma factors that bind to the RNA polymerase and give it promotor specificity. Sigma factor E (SigE) controls the expression of genes that are essential for Mtb virulence. Analysis of the macrophage transcriptional response indicated that proteins encoded by the sigE regulon are involved in the modulation of the macrophage inflammatory response. We compared the global gene expression of mouse bone marrow macrofages infected with H37Rv and SigE to the gene expression profile of the uninfected macrophages.
Project description:M. tuberculosis H37Rv was grown in vitro in five different conditions, including four stress conditions that could mimic what M. tuberculosis may experience in macrophages. The gene expression profiling was studied. Methods: Mycobacterium tuberculosis H37Rv strain was grown under 5 different conditions, in duplicate. RNAseq was performed. The gene expression was compared and Differential Expression was analyzed. Results: The gene expression profiling in microaerophilic and stationary phase conditions were the most similar while the profiling in acidic condition was the closest to exponential phase condition. An average 1050 genes were differentially transcribed in each stress condition except for the acidic stress, which had less than 200 genes differentially regulated.
Project description:New strategies are required to reduce the worldwide burden of tuberculosis. Intracellular survival and replication of Mycobacterium tuberculosis after macrophage phagocytosis is a fundamental step in the complex host-pathogen interactions that lead to granuloma formation and disease. Greater understanding of how the bacterium survives and thrives in these environments will inform novel drug and vaccine discovery programmes. Here, we use in-depth RNA sequencing of Mycobacterium bovis BCG from human THP-1 macrophages to describe the mycobacterial adaptations to the intracellular environment. We identify 329 significantly differentially regulated genes, highlighting cholesterol catabolism, methyl-citrate cycle and iron homeostasis as important for mycobacteria inside macrophages. Focused analysis of PE/PPE and cytochrome P450 gene families highlight additional pathways that are upregulated (35 and five respectively) 24h after infection. Comparison of the intracellular transcriptome to gene essentiality and immunogenicity studies identified 15 potential targets that are both required for intracellular survival and induced on infection, and eight genes upregulated that have been demonstrated to be immunogenic in TB patients. Further insight into these new and established targets will support drug and vaccine development efforts.