Pulmonary Epithelial Injury Impairs Innate Defense and Reprograms Macrophage Function, Reducing Early Mycobacterium tuberculosis Clearance
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE298041 | GEO | 2025/11/18
REPOSITORIES: GEO
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2013-06-28 | E-GEOD-48027 | biostudies-arrayexpress
Project description:The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria: Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC = Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis
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2014-01-28 | E-GEOD-54442 | biostudies-arrayexpress
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2013-12-31 | E-GEOD-44848 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis (Mtb) is one of the most successful pathogens in human history and remains the second leading cause of death from an infectious agent worldwide. The major reason of Mtb success principally relies on its ability to perfectly adapt to the host, by establishing latent infection and evading from the control driven by immune system. Accordingly, both innate and adaptive immune responses are required to control TB progression and pathogenesis and in particular dendritic cells (DC), as professional antigen presenting cells, are one of the major cellular effectors of the anti-mycobacterial response. In this context, we performed a microarray analysis to characterize the de-regulation of cellular miRNAs during Mtb infection of human DC. Human DC were prepared from human peripheral blood mononuclear cells of anonymous healthy blood donors and infected with Mtb for 3, 8 and 24 hours. This data set contains the global miRNA expression profiling in uninfected and Mtb-infected DC cultures to identify altered signature of miRNAs potentially implicated in Mtb-mediated immune evasion strategies.
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2014-01-28 | GSE54442 | GEO