Project description:Mycobacterium tuberculosis (Mtb)-induced shifts in macrophage metabolism are an accepted central infection paradigm. Mtb-infected murine lung tissue exhibits gene expression changes consistent with classic Warburg metabolism and Mtb-infected murine macrophages undergo TCA cycle remodeling. Human macrophages also respond energetically to Mtb infection, however, interestingly the phenotypic nature of this response appears to vary depending on the viability of infection. Despite the overwhelming consensus that metabolic changes are critical to the host response to infection, we have little understanding of the metabolic transcriptional landscape of virulent Mtb-infected human alveolar macrophages (AM), the sentinel pulmonary immune cell during Mtb infection. Further still, whether the human AM undergoes glycolytic reprogramming and TCA cycle remodeling during virulent Mtb infection remains undefined; as is suggested to occur in circulating Mtb-infected human macrophages. Here, we aimed to characterise the metabolic transcriptional profile of virulent Mtb-infected human AM. We hypothesised that infection would induce the transcriptome of Warburg metabolism (characterised by aerobic glycolysis), TCA cycle remodeling, and reduce expression of genes involved in mitochondrial oxidative phosphorylation (OXPHOS).
Project description:Transcriptomics on lung-resident CD8+ T cells reveals how global gene expression patterns diverge over the course of infection with virulent Mtb and non-pathogenic BCG strains. CD8+ T cells from Mtb-infected animals respond with a stronger activation profile than cells from BCG-infected animals, promoting a more inflammatory gene expression profile that contributes to increased indicators of T cell exhaustion, apoptosis and metabolic reprogramming. These data provide new insights into the differential regulation of T cell immunity in virulent and non-virulent Mycobacterial infections.
Project description:We examined the microRNA profiles of THP-1 macrophages upon the MTB infection of (1) Beijing/W and non-Beijing/W clinical strains, and (2) susceptible and multidrug-resistant (MDR-) MTB strains. THP-1 cells were induced differentiation into a macrophage phenotype. Then cells were infected with three MDR (INHR, RIFR) Beijing/W, three sensitive (INHS, RIFS) Beijing/W, three MDR(INHR, RIFR) non-Beijing/W, and three sensitive (INHS, RIFS) non-Beijing/W strains. Total RNA were extracted and transfered into cDNA for miRNA profile analysis. Non-infected cells were used as control.
Project description:ILCs were sorted from the lungs of Mtb infected mice at 5 and 14 days post infection and subjected to sc-RNA sequencing to determine gene signature profile
Project description:The peritoneal macrophages were infected with Mtb H37Rv for 4 hours, and the miRNA expression profile were analyzed with deep sequencing.
Project description:Global gene expressions of Mtb-infected mouse lungs were compared between with and without PDE4 inhibitor treatment. A lot of host genes are differentially expressed 21d and 28d post-Mtb infection. PDE4 inhibitor, however, downregulate 10% of genes among those and genes differentially regulated by PDE4 inhibitor are mainly involved immune response. Total RNA was isolated from Mtb-infected mouse lungs with or without CC-3052 (25 mg/kg/day) using Trizol reagent and gene profile was analyed using Affymetrix mouse ST 1.0
Project description:Purpose: The goal of this study was the transcriptome high-throughput data analysis of spleen cells from mice infected with a virulent strain of mycobacterium (H37rv) and either fed ad libitum (AL) or caloric restricted (CR) Methods: Spleen cell total RNA profile of 17 weeks old mice (1. MTB infected, Ad libitum fed; 2. MTB infected, Caloric restricted; 3. Not infected, Ad libitum fed; 4. Not infected, Caloric restricted; a pool of 5 animals per group) were generated by deep sequencing, in triplicate, using TruSeq Stranded Total RNA Illumina technology Results: Principal component analysis and unsupervised clustering showed that the RNA-seq profiles of spleen cells from these four groups of mice were clearly distinct and infection was the major force affecting gene expression, with 67% of variance coming from the infection status and another 23% variance being dependent on caloric intake . When directly comparing AL versus CR MTB infected spleens, 628 genes were found differentially expressed. Supervised hierarchical clustering based on the expression of these 628 genes was able to unveil the unique transcriptional profile of CR MTB infected mice compared to both AL MTB infected and Not infected mice. Coclusions: Caloric restriction is able to affect the expression of a significant number of genes in spleen cells isolated from mice infected with MTB. The study of biological process enrichements highlights relevant immune-related regulation in these animals, than may be at the base of the higher capacity of caloric restricted, compared to ad libitum fed, animals to resist MTB infection.
Project description:The C57B/6 mice were infected with Mtb H37Rv (CFU=200) for 28 days, and the miRNA expression profile from lung tissues were analyzed with deep sequencing.
Project description:Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study is to compare gene expression (RNA-seq) profile between Mtb infected Fth+/+ and Fth-/- mice at 9 weeks post Mtb infection. Gene expression analysis demonstrated an essential role for FtH in mitochondrial function and maintenance of central intermediary metabolism in vivo