Project description:CD4+ T cells were sorted from the lungs of differentially treated mice and subjected to RNA sequencing to determine global gene signature profile
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: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: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.
Project description:To gain holistic of the immune landscape of lesions following infection with Mycobacterium tuberculosis, we aerosol infected C3HeB/FeJ mice with 1-3 CFU of Mtb (SA161 strain). 35 days following infection, lungs were harvested and fixed, then embedded and frozed in OCT. 10um sections were obtained, classified as necrotic or non-necrotic by visual inspection and brightfield imaging, then stained with markers delineating lesions, and subsequently processed and sampled using the nanostring GeoMX platform. We then compared the transcriptional environment of necrotic vs non-necrotic lesions
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
Project description:CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis (Mtb) is unknown. We compared transcriptomes of purified lung CD8 T cells from Mtb infected WT and MHCII KO mice. Using two independent models, we validated RNA-seq results and showed that CD4 T cell help enhanced CD8 effector functions and prevented CD8 T cell exhaustion. We demonstrated synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restricted intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.
Project description:The virulence of Mycobacterium tuberculosis (Mtb), either as mostly aggregates or single cells (Mtb-SC), was compared using a rabbit model of pulmonary infection. Our hypothesis is that aggregation contributes to enhanced virulence of Mtb. Rabbit lung transcriptome was analyzed by RNAseq to identify differentially regulated gene networks and pathways between Mtb-AG and Mtb-SC infection of rabbit lungs soon after seeding of the bacteria (24 hours post-inoculation).