Intracellular transcriptional adaptation of Mycobacterium tuberculosis complex (MTC) clinical isolates inside resting murine macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mycobacterium tuberculosis
PROVIDER: GSE21112 | GEO | 2010/07/09
SECONDARY ACCESSION(S): PRJNA129703
REPOSITORIES: GEO
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Project description:This study uses microarray analyses to examine transcriptional responses of Mycobacterium tuberculosis complex clinical isolates to phagosomal cues encountered inside resting murine bone marrow-derived macrophages 24hr post-infection. Transcript levels of intracellular mycobacteria were compared to extracellular bacteria of the same strain (An aliquot of the inoculum used to infect macrophages was incubated in the absence of macrophages for 24hr in an identical flask). Set of arrays that are part of repeated experiments Keywords: Biological Replicate Biological Replicate Computed
2010-07-09 | E-GEOD-21112 | biostudies-arrayexpress
Project description:This study uses microarray analyses to examine transcriptional responses of Mycobacterium tuberculosis complex clinical isolates to phagosomal cues encountered inside activated (IFN-gamma+LPS) murine bone marrow-derived macrophages 24hr post-infection. Transcript levels of intracellular mycobacteria were compared to extracellular bacteria of the same strain (An aliquot of the inoculum used to infect macrophages was incubated in the absence of macrophages for 24hr in an identical flask). Set of arrays that are part of repeated experiments Keywords: Biological Replicate
2010-07-09 | GSE21113 | GEO
Project description:This study uses microarray analyses to examine transcriptional responses of Mycobacterium tuberculosis complex clinical isolates to phagosomal cues encountered inside activated (IFN-gamma+LPS) murine bone marrow-derived macrophages 24hr post-infection. Transcript levels of intracellular mycobacteria were compared to extracellular bacteria of the same strain (An aliquot of the inoculum used to infect macrophages was incubated in the absence of macrophages for 24hr in an identical flask). Set of arrays that are part of repeated experiments Keywords: Biological Replicate Biological Replicate Computed
2010-07-09 | E-GEOD-21113 | biostudies-arrayexpress
Project description:Pathogenic mycobacteria subvert immune responses to survive and replicate in macrophages. Mycobacterial cell wall components are sensed by several C-type lectin receptors, including MINCLE, the receptor for the cord factor trehalose-6,6-dimycolate (TDM). Regulation of innate immune cells relies on miRNAs, some of which are induced by mycobacterial ligands. Thus, MTB may exploit host miRNAs to establish its niche in macrophages. Here, we have employed conditional knockout mice for the microprocessor component DGCR8 to investigate the impact of miRNAs on the macrophage response to the mycobacterial cord factor. Deletion of DGCR8 during differentiation of macrophages from bone marrow progenitors significantly reduced the cell yield, but did not interfere with macrophage differentiation as determined by typical surface marker expression and phagocytic capacity. DGCR8-deficient macrophages expressed reduced levels of constitutive and TDM-inducible miRNAs, yet in turn accumulated primary miRNA transcripts. RNAseq revealed a modest type I interferon (IFN) signature in resting DGCR8-deficient macrophages. Stimulation of DGCR8-deficient macrophages with TDM induced overshooting and prolonged expression of interferon response genes, which was associated with enhanced expression of IFNb and could be largely prevented by antibodies to type I interferon. In turn, exogenous IFNb upregulated CXCL10 and CD69 to similar levels in control and DGCR8-deficient macrophages, indicating that signaling downstream of the type I IFN receptor was unaltered. Infection with live Mycobacterium bovis Bacille Calmette-Guerin (BCG) replicated the enhanced interferon response of DGCR8-deficient macrophages. Together, our results reveal an essential role for DGCR8 in curbing IFNb expression and IFN-dependent macrophage activation by mycobacteria.
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Project description:The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Although some Francisella determinants of intracellular growth have been identified, much remains to be understood about the pathogenesis of this organism. In particular, how Francisella responds to its intracellular environment could provide clues about its intracellular biology and reveal pathogenic determinants based on their intracellular expression profiles. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages. Phagocytosed bacteria rapidly responded to their intracellular environment and progressively altered their transcriptional profile over time. Differential gene expression profiles were revealed that correlated with specific intracellular locations of the bacteria. Upregulation of general and oxidative stress response genes was a hallmark of the early phagosomal and late endosomal stages, while induction of a subset of transport and metabolic genes characterized the cytosolic replication stages. Expression of the Francisella Pathogenicity Island (FPI) genes, the functions of which are associated with intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci putatively encoding hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated during the intracellular cycle. In-frame deletion of FTT0383, the Schu S4 ortholog of fevR, of FTT0369c or FTT1676 abolished the ability of Schu S4 to either survive or proliferate intracellularly, demonstrating that bacterial factors of intracellular pathogenesis can be identified based on their intracellular expression profile. In conclusion, establishing the intracellular transcriptome of Francisella has revealed important aspects of its intracellular biology and identified novel virulence determinants of this pathogen. Keywords: Time series Intracellular cycle within primary murine macrophages using the time series of zero, one, two, four, eight, twelve, sixteen and twenty-four hours
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Project description:This study uses microarray analyses to examine baseline gene expression profiles for Mycobacterium tuberculosis complex clinical isolates relative to reference strain CDC1551 during log phase growth in vitro in 7H9 broth. For this in vitro analyses, log-phase mycobacteria in starter cultures grown to mid-log from frozen stocks were inoculated into 7H9-OADC medium in 25-cm2 vented flasks at an OD of ~0.05 and grown without shaking for ~1 week to an OD of ~0.5-0.6.
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Project description:This study uses microarray analyses to examine baseline gene expression profiles for Mycobacterium tuberculosis complex clinical isolates relative to reference strain CDC1551 during log phase growth in vitro in 7H9 broth. For this in vitro analyses, log-phase mycobacteria in starter cultures grown to mid-log from frozen stocks were inoculated into 7H9-OADC medium in 25-cm2 vented flasks at an OD of ~0.05 and grown without shaking for ~1 week to an OD of ~0.5-0.6. Computed
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Project description:Resident tissue macrophages (RTMs) are organ-specialized phagocytes responsible for the maintenance and protection of residing tissue. It is well established that tissue diversity is reflected by the heterogeneity of RTMs origin and phenotype. However, much less is known about tissue-specific phagocytic macrophage functions. Here, using quantitative proteomics approach, we identify cathepsins as key determinants of phagosome maturation in primary peritoneal, lung and brain resident macrophages. The data further uncover cathepsin K (CtsK) as a molecular marker for lung phagosomes required for intracellular protein and collagen degradation. Pharmacological blockade of CtsK activity diminished phagosomal proteolysis and collagenolysis in lung resident macrophages. Furthermore, pro-fibrotic TGF-β negatively regulated CtsK-mediated phagosomal collagen degradation independently from classical endocytic proteolytic pathways. In humans, phagosomal CtsK activity was reduced in lung COPD macrophages and lung macrophages exposed to cigarette smoke extract. Taken together, this study provides a comprehensive map of how peritoneal, lung and brain tissue environment shapes phagosomal composition of resident macrophages, revealing CtsK as a key molecular determinant of lung phagosomes contributing to phagocytic collagen clearance in lungs.
2023-01-18 | PXD033010 | Pride
Project description:The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Although some Francisella determinants of intracellular growth have been identified, much remains to be understood about the pathogenesis of this organism. In particular, how Francisella responds to its intracellular environment could provide clues about its intracellular biology and reveal pathogenic determinants based on their intracellular expression profiles. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis subsp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages. Phagocytosed bacteria rapidly responded to their intracellular environment and progressively altered their transcriptional profile over time. Differential gene expression profiles were revealed that correlated with specific intracellular locations of the bacteria. Upregulation of general and oxidative stress response genes was a hallmark of the early phagosomal and late endosomal stages, while induction of a subset of transport and metabolic genes characterized the cytosolic replication stages. Expression of the Francisella Pathogenicity Island (FPI) genes, the functions of which are associated with intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci putatively encoding hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated during the intracellular cycle. In-frame deletion of FTT0383, the Schu S4 ortholog of fevR, of FTT0369c or FTT1676 abolished the ability of Schu S4 to either survive or proliferate intracellularly, demonstrating that bacterial factors of intracellular pathogenesis can be identified based on their intracellular expression profile. In conclusion, establishing the intracellular transcriptome of Francisella has revealed important aspects of its intracellular biology and identified novel virulence determinants of this pathogen. Keywords: Time series
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