Transcriptome of human monocyte-derived macrophages infected with live-Mycobacterium leprae
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE162416 | GEO | 2021/04/16
REPOSITORIES: GEO
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Project description:Leprosy is major public health problem in developing countries. M. leprae infects human macrophages and Schwann cells leading to a chronic disease. Leprosy studies are constrained due to the lack of in vitro growth system for M. leprae. Moreover, the overall pathogenesis is poorly understood although the expression of some pro-inflammatory cytokines is associated with nerve damage that occurs during the infection. PBMC may participate of the host response to M. leprae infection leading to the inflammatory profile. We aimed to investigate the global human gene expression profile of human PBMC exposed to M. leprae for 4 H. Due to the reduced supply of M. leprae our study was restricted to three chips, including a dye-swap set. Our analysis revealed gene expression differences in cell receptors, NF-kB signaling and oxidative stress response. The results were confirmed by Real-time PCR and flow-cytometry and point to new insights into the molecular events resulted from host-pathogen interaction We analyzed 3 oligo-human chips, 10K elements each, spotted in duplicates. Two chips were replicas and one a dye-swap
2007-09-01 | E-GEOD-5765 | biostudies-arrayexpress
Project description:In attempt to understand M.leprae interaction with the human host, Applied Biosystems microarrays containing 30,865 probles were used to identify modulated genes in primary human Schwann Cells (SC) infected with live M. leprae at two early time points, 24 and 48 hours. A total of 4 independent experimental samples were prepared which were hybridized to two replicate microarrays each.The four experimental samples included both uninfected and M. leprae infected Schwann cells at both 24 and 48 hours.
2012-06-30 | E-GEOD-35423 | biostudies-arrayexpress
Project description:The initial interaction between a microbial pathogen and the host immune response influences the outcome of the battle between the host and the foreign invader. Leprosy, caused by the obligate intracellular pathogen Mycobacterium leprae, provides a model to study relevant human immune responses. Previous studies have adopted a targeted approach to investigate host response to M. leprae infection, focusing on the induction of specific molecules and pathways. By measuring the host transcriptome triggered by M. leprae infection of human macrophages, we were able to detect a host gene signature 24–48 hours after infection characterized by specific innate immune pathways involving the cell fate mechanisms autophagy and apoptosis. The top upstream regulator in the M. leprae-induced gene signature was NUPR1, which is found in the M. leprae-induced cell fate pathways. The induction of NUPR1 by M. leprae was dependent on the production of the type I interferon (IFN), IFN-β. Furthermore, NUPR1 mRNA and protein were upregulated in the skin lesions from patients with the multibacillary form of leprosy. Together, these data indicate that M. leprae induces a cell fate program which includes NUPR1 as part of the host response in the progressive form of leprosy
2019-01-31 | GSE120959 | GEO
Project description:Leprosy is major public health problem in developing countries. M. leprae infects human macrophages and Schwann cells leading to a chronic disease. Leprosy studies are constrained due to the lack of in vitro growth system for M. leprae. Moreover, the overall pathogenesis is poorly understood although the expression of some pro-inflammatory cytokines is associated with nerve damage that occurs during the infection. PBMC may participate of the host response to M. leprae infection leading to the inflammatory profile. We aimed to investigate the global human gene expression profile of human PBMC exposed to M. leprae for 4 H. Due to the reduced supply of M. leprae our study was restricted to three chips, including a dye-swap set. Our analysis revealed gene expression differences in cell receptors, NF-kB signaling and oxidative stress response. The results were confirmed by Real-time PCR and flow-cytometry and point to new insights into the molecular events resulted from host-pathogen interaction Keywords: Modulation of human PBMC gene expression by M. leprae
2007-09-01 | GSE5765 | GEO
Project description:In an attempt to understand M. leprae interaction with the human host, Stanford Genomics HEEBO Arrays were use to identify modulated genes in primary human Schwann cells infected with live M. leprae at a MOI of 100:1 for 24 hours. Dual channel competitive hybridizations between M. leprae infected and non infected Schwann cells including 3 independent biological replicates and a technical replicate in the form of dye swap.
2013-01-03 | E-GEOD-40950 | biostudies-arrayexpress
Project description:In attempt to understand M.leprae interaction with the human host, Applied Biosystems microarrays containing 30,865 probles were used to identify modulated genes in primary human Schwann Cells (SC) infected with live M. leprae at two early time points, 24 and 48 hours.
2012-07-01 | GSE35423 | GEO
Project description:In an attempt to understand M. leprae interaction with the human host, Stanford Genomics HEEBO Arrays were use to identify modulated genes in primary human Schwann cells infected with live M. leprae at a MOI of 100:1 for 24 hours.
2013-01-03 | GSE40950 | GEO
Project description:Leprosy is a human infectious disease caused by Mycobacterium leprae. A strong host genetic contribution to leprosy susceptibility is well established. However, the modulation of the transcriptional response to infection and the mechanism(s) of disease control are poorly understood. To address this gap in knowledge of leprosy pathogenicity, we conducted a genome-wide search for expression quantitative trait loci (eQTL) that are associated with transcript variation –– before and after stimulation with M. leprae sonicate in whole blood cells. We show that M. leprae antigen stimulation mainly triggered the upregulation of immune related genes and that a substantial proportion of the differential gene expression is genetically controlled. Indeed, using stringent criteria, we identified 318 genes displaying cis-eQTL at an FDR of 0.01, including 66 genes displaying response-eQTL (reQTL), i.e. cis-eQTL that showed significant evidence for interaction with the M. leprae stimulus. Such reQTL correspond to regulatory variations that affect the interaction between human whole blood cells and M. leprae sonicate, and thus likely between the human host and M. leprae bacilli. We found that reQTL are significantly enriched among binding sites of transcription factors that are activated in response to infection, and that they were enriched among single nucleotide polymorphisms (SNPs) associated with susceptibility to leprosy per se and Type-I Reaction, as well as SNPs targeted by recent positive selection. Our study suggests that natural selection shaped our genomic diversity to face pathogen exposure including M. leprae infection.
2017-07-07 | GSE100853 | GEO
Project description:Mycobacterium leprae, the causative agent of leprosy, an obligate intracellular pathogen has the ability to survive and grow for extended periods within phagocytes and Schwann cells. M. leprae genome analysis predicts a highly degraded genome resulting in a significant loss of its genomic coding capacity. Detailed dynamics of carbon sources for energy utilization and growth of M. leprae is unclear. This study, therefore, presents M. leprae transcriptome during in vivo growth and ex vivo stationary phases, and explores metabolic pathways relevant to its growth from global gene expression data. This report provides a glimpse of some of M. leprae nutritional requirements for growth, which most likely, needs to be supplemented, in an axenic growth media.
2022-01-01 | GSE188532 | GEO
Project description:Approximately half of M. lepraeâ??s transcriptome consists of inactive gene products. This has an impact on overall energy and resource consumption without potential benefit to this organism. However, multiple translational â??silencingâ?? mechanisms are present, reducing additional energy and resource expenditure required for protein production from these transcripts. The Mycobacterium leprae genome has less than 50% coding capacity and 1,133 pseudogenes. Preliminary evidence suggests that some pseudogenes are expressed. Therefore, defining pseudogene transcriptional and translational potentials should increase our understanding of their impact on M. leprae physiology. To address this, M. leprae was purified from the granulomatous hind footpad tissue of four individual nu/nu nude mice six months post-infection. M. leprae whole genome DNA microarrays representing the 1,614 annotated ORFs and 1,133 identified pseudogenes, were obtained from the Leprosy Research Support and Maintenance of an Armadillo Colony Post-Genome Era, Part I: Leprosy Research Support Contract (NO1 AI-25469) at Colorado State University. To validate 20% of genes positive by microarray analysis, RT-PCR was performed. Results of this study Gene expression analysis identified transcripts from 49% of all M. leprae genes including 57% of all ORFs and 43% of all pseudogenes in the genome. Pseudogenes were randomly distributed throughout the chromosome. Factors resulting in pseudogene transcription included: 1) co-orientation of transcribed pseudogenes with transcribed ORFs within or exclusive of operon-like structures; 2) the paucity of intrinsic stem-loop transcriptional terminators between transcribed ORFs and downstream pseudogenes; and 3) predicted pseudogene promoters. Mechanisms for translational silencing of pseudogene transcripts included the lack of both translational start codons and strong Shine-Dalgarno sequences. Transcribed pseudogenes also contained multiple in-frame stop codons and high Ka/Ks ratios, compared to that of homologs in M. tuberculosis and ORFs in M. leprae. A pseudogene transcript containing an active promoter, strong SD site, a start codon, but containing two in frame stop codons yielded a protein product when expressed in E. coli. Approximately half of M. leprae's transcriptome consists of inactive gene products consuming energy and resources without potential benefit to M. leprae. Presently it is unclear what additional detrimental affect(s) this large number of inactive mRNAs has on the functional capability of this organism. Translation of these pseudogenes may play an important role in overall energy consumption and resultant pathophysiological characteristics of M. leprae. However, this study also demonstrated that multiple translational silencing mechanisms are present, reducing additional energy and resource expenditure required for protein production from the vast majority of these transcripts. The overall design of this study was to identify the transcriptome of M. leprae in the granulomatous tissue of the mouse hind foot pad 6 months post infection.
2010-06-24 | E-GEOD-17191 | biostudies-arrayexpress