Project description:In-vivo Gene Signatures of Mycobacterium tuberculosis In C3HeB/FeJ Mice In this experiment we have compared Mtb transcriptomics in-vivo, using samples derived from chronically infected C3HeB/FeJ mice, which produce human like caseating lesions, unlike other murine species, to Mtb cultured in-vitro. Similarly, the genome-wide expression of MtbdeldosR, MtbdeldosS and MtbdeldosT mutants is also compared between lungs from C3HeB/FeJ mice and in-vitro culturing.
Project description:Neutrophils are accumulated in mouse lungs following Mycobacterium tuberculosis infections. Increased influx of neutrophils is associated with increased susceptibility to disease, but the underlying mechanisms of neutrophil mediated Tuberculosis disease pathogenesis is poorly understood. To understand the transcriptomic differences between resistant (C57 BL/6) and susceptible (C3HeB/FeJ) mouse lung neutrophils, we sorted them at Day 29 post infection and analyzed them by bulk mRNA sequencing.
Project description:Only a minority of M. tuberculosis-infected individuals progress to tuberculosis, however the early immune mechanisms determining outcome are unclear. C3HeB/FeJ mice display high, partially type I IFN-dependent, tuberculosis susceptibility, compared to relatively tuberculosis-resistant C57BL/6 mice. Using bulk and scRNA-seq over the first weeks of M. tuberculosis infection, we describe an unexpected, higher early pulmonary type I IFN response in C57BL/6 than C3HeB/FeJ mice, accompanying more pronounced early monocyte-derived macrophage (MDM) accumulation and lesion formation. The C57BL/6 type I IFN response plateaued with formation of extensive CD4+ T cell-MDM interactions in lesions, accompanied by high expression of T cell-attractant chemokines by MDMs. Conversely, delayed immune initiation in C3HeB/FeJ mice preceded rapid domination of lesions by inflammatory neutrophils, depletion of which enhanced CD4+ T cell-MDM interactions. Type I IFNs unexpectedly promoted early bacterial replication and limited lesion CD4+ T cell numbers in both C57BL/6 and C3HeB/FeJ mice, while pronounced later effects on inflammatory neutrophil activation were observed in C3HeB/FeJ, suggestive of context-dependent effects of type I IFNs during M. tuberculosis infection.
Project description:Only a minority of M. tuberculosis-infected individuals progress to tuberculosis, however the early immune mechanisms determining outcome are unclear. C3HeB/FeJ mice display high, partially type I IFN-dependent, tuberculosis susceptibility, compared to relatively tuberculosis-resistant C57BL/6 mice. Using bulk and scRNA-seq over the first weeks of M. tuberculosis infection, we describe an unexpected, higher early pulmonary type I IFN response in C57BL/6 than C3HeB/FeJ mice, accompanying more pronounced early monocyte-derived macrophage (MDM) accumulation and lesion formation. The C57BL/6 type I IFN response plateaued with formation of extensive CD4+ T cell-MDM interactions in lesions, accompanied by high expression of T cell-attractant chemokines by MDMs. Conversely, delayed immune initiation in C3HeB/FeJ mice preceded rapid domination of lesions by inflammatory neutrophils, depletion of which enhanced CD4+ T cell-MDM interactions. Type I IFNs unexpectedly promoted early bacterial replication and limited lesion CD4+ T cell numbers in both C57BL/6 and C3HeB/FeJ mice, while pronounced later effects on inflammatory neutrophil activation were observed in C3HeB/FeJ, suggestive of context-dependent effects of type I IFNs during M. tuberculosis infection.
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Lupulone treated strains. Goal was to determine the effects of Lupulone against Mycobacterium tuberculosis H37Rv strains.
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Linezolid treated strains. Goal was to determine the effects of Linezolid against Mycobacterium tuberculosis H37Rv strains.
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Lupulone treated strains. Goal was to determine the effects of Lupulone against Mycobacterium tuberculosis H37Rv strains. Two-condition experiment,control DMSO treated strains vs. Lupulone treated strains. Biological replicates: 2 control replicates, 2 Lupulone replicates.
Project description:Transcriptional profiling of Mycobacterium tuberculosis H37Rv strains comparing control DMSO treated strains with Linezolid treated strains. Goal was to determine the effects of Linezolid against Mycobacterium tuberculosis H37Rv strains. Two-condition experiment,control DMSO treated strains vs. Linezolid treated strains. Biological replicates: 2 control replicates, 2 Linezolid replicates.
