Transcriptional response of Mycobacterium tuberculosis in mouse peritoneal macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis H37Rv
PROVIDER: GSE158465 | GEO | 2020/09/24
REPOSITORIES: GEO
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Project description:This study was conducted to descripe transcriptomic changes of M.tuberculosis during neutrophil infection
2019-11-09 | GSE140156 | GEO
Project description:Host macrophage transcriptional responses to intracellular pathogens remain poorly characterized. We screened transcriptional enhancers engaged in response to M. tuberculosis (Mtb) infection by ChIPseq analysis of histone H3 lysine 4 monomethylation (H3K4me1). De novo monomethylation during infection was associated with genes implicated in host defense and apoptosis. These regions were enriched for binding sites for ETS transcription factor family members and response elements for nuclear receptors, including liver X receptors (LXRs) and peroxisomal proliferator activated receptors (PPARs), many of which were encompassed by transposable elements. LXRa expression was strongly induced by infection, whereas that of PPARs was unaffected. LXR DNA binding and NCoR corepressor recruitment increased proportionately in infected cells but coactivator association was unchanged, consistent with a lack of induction of endogenous agonists. However, treatment of infected cells with LXR agonist T0901317 strongly increased coactivator recruitment and induced a gene expression program characterized by enhanced innate immune signaling and lipid metabolism. Remarkably, T0901317 treatment selectively induced apoptosis in infected macrophages, and was accompanied by Mtb death, reducing mycobacterial burden 18-fold relative to vehicle 5d after infection. These studies define macrophage transcriptional responses to Mtb infection, and suggest that tissue-specific LXRa agonists may be efficacious in clinical management of tuberculosis.
2016-01-31 | GSE64335 | GEO
Project description:Transcriptional response of Mycobacterium tuberculosis in mouse peritoneal macrophages
| PRJNA665269 | ENA
Project description:During lung infection Mycobacterium tuberculosis (Mtb) resides in macrophages and subverts the bactericidal mechanisms of these professional phagocytes. In this work we have analyzed by DNA microarray technique the global transcription profile of Mtb infecting primary human macrophages in order to identify putative bacterial pathogenic factors that can be relevant for the intracellular survival of Mtb. Keywords: time course We compared the global gene expression of the H37Rv strain of Mtb after 4 hours and 24 hours of infection of human macrophage-like THP-1 cells with the gene expression profile of the strain growing exponentially in broth cultures.
2010-05-27 | E-GEOD-6209 | biostudies-arrayexpress
Project description:BackgroundTuberculosis (TB), a bacterial infection caused by Mycobacterium tuberculosis (Mtb) remains a significant health problem worldwide with a third of the world population infected and nearly nine million new cases claiming 1.1 million deaths every year. The outcome following infection by Mtb is determined by a complex and dynamic host-pathogen interaction in which the phenotype of the pathogen and the immune status of the host play a role. However, the molecular mechanism by which Mtb strains induce different responses during intracellular infection of the host macrophage is not fully understood. To explore the early molecular events triggered upon Mtb infection of macrophages, we studied the transcriptional responses of murine bone marrow-derived macrophages (BMM) to infection with two clinical Mtb strains, CDC1551 and HN878. These strains have previously been shown to differ in their virulence/immunogenicity in the mouse and rabbit models of pulmonary TB.ResultsIn spite of similar intracellular growth rates, we observed that compared to HN878, infection by CDC1551 of BMM was associated with an increased global transcriptome, up-regulation of a specific early (6 hours) immune response network and significantly elevated nitric oxide production. In contrast, at 24 hours post-infection of BMM by HN878, more host genes involved in lipid metabolism, including cholesterol metabolism and prostaglandin synthesis were up-regulated, compared to infection with CDC1551.In association with the differences in the macrophage responses to infection with the 2 Mtb strains, intracellular CDC1551 expressed higher levels of stress response genes than did HN878.ConclusionsIn association with the early and more robust macrophage activation, intracellular CDC1551 cells were exposed to a higher level of stress leading to increased up-regulation of the bacterial stress response genes. In contrast, sub-optimal activation of macrophages and induction of a dysregulated host cell lipid metabolism favored a less stressful intracellular environment for HN878. Our findings suggest that the ability of CDC1551 and HN878 to differentially activate macrophages during infection probably determines their ability to either resist host cell immunity and progress to active disease or to succumb to the host protective responses and be driven into a non-replicating latent state in rabbit lungs.
| S-EPMC3317440 | biostudies-literature
Project description:Mycobacterium tuberculosis (Mtb) is well adapted to survive in macrophages and usually subverts the bactericidal mechanisms of these professional phagocytes. The adaptation of Mtb to the intracellular life depends on its ability to regulate the expression of its genes. Among the most important bacterial transcription activators are the sigma factors that bind to the RNA polymerase and give it promotor specificity. Sigma factor E (SigE) controls the expression of genes that are essential for Mtb virulence. Analysis of the macrophage transcriptional response indicated that proteins encoded by the sigE regulon are involved in the modulation of the macrophage inflammatory response. We compared the global gene expression of mouse bone marrow macrofages infected with H37Rv and SigE to the gene expression profile of the uninfected macrophages.
2010-05-25 | E-GEOD-7871 | biostudies-arrayexpress
Project description:Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and -irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as RSAD2, IFIT1/2/3 and RIG-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.
2016-10-18 | GSE88801 | GEO
Project description:Mycobacterium tuberculosis (Mtb) is well adapted to survive in macrophages and usually subverts the bactericidal mechanisms of these professional phagocytes. The adaptation of Mtb to the intracellular life depends on its ability to regulate the expression of its genes. Among the most important bacterial transcription activators are the sigma factors that bind to the RNA polymerase and give it promotor specificity. Sigma factor E (SigE) controls the expression of genes that are essential for Mtb virulence. Analysis of the macrophage transcriptional response indicated that proteins encoded by the sigE regulon are involved in the modulation of the macrophage inflammatory response. Keywords: Comparison of responses to infections
2008-03-27 | GSE7871 | GEO
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug Rifampicin. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
2021-12-15 | GSE166622 | GEO
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug Bedaquiline. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
2021-12-15 | GSE166546 | GEO