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Mouse transcriptome reveals novel signatures of protection and pathogenesis in human tuberculosis [blood]

ABSTRACT: Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis

ORGANISM(S): Mus musculus

PROVIDER: GSE137092 | GEO | 2020/01/09

REPOSITORIES: GEO

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Mouse transcriptome reveals novel signatures of protection and pathogenesis in human tuberculosis [lung]

Project description:Characterisation of blood and lung global transcriptional responses to Mycobacterium tuberculosis infection in distinct mouse models of Tuberculosis

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Mouse transcriptome reveals novel signatures of protection and pathogenesis in human tuberculosis [blood]

Project description:Mouse transcriptome reveals novel signatures of protection and pathogenesis in human tuberculosis [blood]

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Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis.

Project description:Although mouse infection models have been extensively used to study the host response to Mycobacterium tuberculosis, their validity in revealing determinants of human tuberculosis (TB) resistance and disease progression has been heavily debated. Here, we show that the modular transcriptional signature in the blood of susceptible mice infected with a clinical isolate of M. tuberculosis resembles that of active human TB disease, with dominance of a type I interferon response and neutrophil activation and recruitment, together with a loss in B lymphocyte, natural killer and T cell effector responses. In addition, resistant but not susceptible strains of mice show increased lung B cell, natural killer and T cell effector responses in the lung upon infection. Notably, the blood signature of active disease shared by mice and humans is also evident in latent TB progressors before diagnosis, suggesting that these responses both predict and contribute to the pathogenesis of progressive M. tuberculosis infection.

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Project description:Mouse transcriptome reveals novel signatures of protection and pathogenesis in human tuberculosis [lung]

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Mouse transcriptome reveals signatures of protection and pathogenesis in human tuberculosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-01-09 | GSE140945 | GEO

Comparison of M. tuberculosis and M. bovis BCG in diluted whole blood cultures

Project description:Despite wide scale vaccination with Mycobacterium bovis BCG, the prevalence of tuberculosis remains high, reflecting the global variable efficacy of this vaccine against adult pulmonary TB. Characterisation of different immune responses to M. tuberculosis and M. bovis BCG would increase understanding of pathology following M. tuberculosis infection or reactivation, and would facilitate the rational design of a new vaccine. Gene expression profiling was conducted on samples from diluted whole blood cultures from three healthy donors following incubation with live mycobacteria for six days. Approximately 8,000 gene entities were at least two-fold up- or down- regulated by the mycobacteria, and both mycobacteria induced similar expression changes in approximately 2,300 genes. Strikingly, many genes exhibited qualitatively different expression patterns, with over 1,000 genes up-regulated in response to M. bovis BCG but not changed by M. tuberculosis. Gene Ontology analysis revealed that the genes which failed to upregulate in M. tuberculosis-infected cultures included a large proportion of genes with lysosomal function. The inhibited up-regulation of expression of IFN-γ-inducible protein 30, acid phosphatase 2, cathepsin B and GM2 ganglioside activator was verified in samples from six biologically independent donors by qRT-PCR. The failure to up-regulate these genes in response to M. tuberculosis may constitute an immune evasion mechanism, preventing intracellular killing and antigen presentation.

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