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Gene expression analysis of mouse alveolar macrophages infected with Mycobacterium tuberculosis isolated from BCG-vaccinated mice [balRNAseq]

ABSTRACT: The aim of this study was to measure the immune response of alveolar macrophages (AMs) from BCG-vaccinated mice to intracellular Mtb infection in vivo. We characterized the transcriptional profile of murine Mtb-infected AMs after aerosol infection by sorting cells from bronchoalveolar lavage fluid and performing low-input RNA-sequencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE212202 | GEO | 2023/11/30

REPOSITORIES: GEO

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Gene expression analysis of alveolar macrophages from BCG-vaccinated and CoMtb mice stimulated ex vivo [exvivoRNAseq]

Project description:The aim of this study was to measure the response of alveolar macrophages (AMs) from BCG-vaccinated mice and mice with CoMtb to LPS, PAM3CSK4, and Mtb stimulation ex vivo.

2023-11-30 | GSE212203 | GEO

Gene expression analysis of Mtb-infected mouse alveolar macrophages from mice lacking Nrf2 in LysM- or CD11c-expressing cells

Project description:The aim of this study was to measure the immune response of alveolar macrophages (AMs) from mice lacking Nrf2 in LysM- or CD11c-expressing cells to intracellular Mtb infection in vivo. We characterized the transcriptional profile of murine Mtb-infected AMs after aerosol infection by sorting cells from bronchoalveolar lavage fluid and performing low-input RNA-sequencing.

2019-06-12 | GSE132185 | GEO

Gene expression analysis of mouse alveolar macrophages infected with Mycobacterium tuberculosis

Project description:The aim of this study was to measure the immune response of alveolar macrophages (AMs) to intracellular Mtb infection in vivo. We characterized the transcriptional profile of murine Mtb-infected AMs after aerosol infection by sorting cells from bronchoalveolar lavage fluid and performing low-input RNA-sequencing. To determine the effect of the transcription factor Nrf2 on this response we also measured the transcriptional profiles of AMs from mice lacking Nrf2.

2019-06-12 | GSE125287 | GEO

RNA-Seq of mouse lung vaccinated with subcutaneous BCG and two novel tuberculosis mucosal boosting nanovaccines

Project description:Mice were left unvaccinated (Naive) or vaccinated with either BCG alone (BCG) or BCG followed by two intranasal boosting of novel nanovaccines Nano-FP1 or Nano-FP2, 12 and 14 weeks later. A group of mice were also administered a 3rd boost of the corresponding nanovaccine 25 weeks after sc. BCG. Mice were sacrificed at 2, 11 and 14 weeks after second boosting, and bronchoalveolar lavage (BAL) and lung parenchyma (Lung) were extracted for RNA-Seq. The group of mice administered a 3rd boosting was the group sacrificed at 14 weeks time-point.

2021-01-28 | E-MTAB-9449 | biostudies-arrayexpress

Prevention of Mycobacterium tuberculosis infection and disease in nonhuman primates following intravenous BCG vaccination

Project description:Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide. Intradermal (ID) vaccination with BCG has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission. Here we show that the route and dose of BCG vaccination alters circulating and lung resident T cells and subsequent protection against Mtb challenge in nonhuman primates (NHP). NHP immunized with BCG by the intravenous (IV) route induced substantially higher antigen-specific CD4 (Th1 or Th17) and CD8 responses in blood, spleen, bronchoalveolar lavage (BAL), and lung lymph nodes compared to the same BCG dose administered by ID or aerosol (AE) routes. Moreover, IV immunization was the only route that induced a high frequency of antigen-specific tissue resident T cells in lung parenchyma. Six months after BCG vaccination, NHP were challenged with virulent Mtb. Strikingly, 9 of 10 NHP that received BCG IV were highly protected, with 6 NHP showing no detectable infection as determined by PET CT imaging, mycobacterial growth, pathology, granuloma formation, or de novo immune responses to Mtb-specific antigens. The finding that BCG IV prevents or significantly limits Mtb infection in NHP has important implications for vaccine development and provides a model for determining immune correlates and mechanisms of protection against TB.

2020-01-01 | GSE139598 | GEO

Gene expression analysis of mouse alveolar macrophages and whole-blood from mice with contained Mycobacterium tuberculosis infection

Project description:The aim of this study was to measure the impact of contained infection with Mycobacterium tuberculosis (CMTB) on the immune response of alveolar macrophages (AMs) to intracellular Mtb infection in vivo and on the circulatory cellularity. We characterized the transcriptional profile of murine AMs in CMTB and control mice by sorting cells from whole-lung lysates and performing RNA-sequencing (samples 1-6). We also characterized the transcriptional profile of murine Mtb-infected AMs after aerosol infection by sorting cells from bronchoalveolar lavage fluid and performing low-input RNA-sequencing (samples 7-12). In order to characterize changes in chromatin accessibility induced by CMTB, we performed ATAC-seq on AMs isolated from control and CMTB mice by BAL (samples 13-18). We also generated whole-blood transcriptomes from mice prior to and following the establishment of CMTB (samples 19-28) in order to characterize the circulatory cellularity.

2020-06-08 | GSE126355 | GEO

A Ferritin Mutant Induces Protective Immunity against Virulent Mycobacterium tuberculosis Infection

Project description:Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with ?bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the ?bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the ?bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the ?bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB. Female C57BL/6 mice were vaccinated subcutaneously with ?bfrB or BCG . At 8 weeks post-vaccination, mice were aerosol infected with Mtb H37Rv. At 4 weeks post infection, mice were sacrificed and lungs were removed. Lung total RNA from vaccinated and Mtb-infected mice was extracted, purified and were processed separately for microarray analysis.

2014-09-01 | E-GEOD-58810 | biostudies-arrayexpress

Single-cell gene expression analysis of pulmonary immune cells from BCG-vaccinated and CoMtb mice [scRNAseq]

Project description:The aim of this study was to measure effect of BCG vaccination or contained Mtb infection (CoMTB) on the expression profile of pulmonary immune cells.

2023-11-30 | GSE212204 | GEO

PBMC expression profiles of BCG vaccine protected infants and of BCG vaccinated infants who develop tuberculosis disease

Project description:Analysis of PBMC from 10 week old infants vaccinated with BCG at birth. During follow-up 26 infants developed tuberculosis (TB) (non-protected by BCG) and 20 infants did not develop TB despite documented exposure (protected by BCG). PBMC were stimulated with media only or reconstituted BCG for 4 and 12 hours. Results provide insight into the mechanisms behind the failure of BCG to protect against disease.

2014-06-30 | GSE20716 | GEO

Anti-mycobacterial activity correlates with altered DNA methylation pattern in immune cells from BCG-vaccinated subjects

Project description:The reason for the largely variable protective effect against TB of the vaccine Bacille Calmette-Guerin (BCG) is not understood. In this study, we investigated whether epigenetic mechanisms are involved in the response of immune cells to the BCG vaccine. We isolated peripheral blood mononuclear cells (PBMCs) from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. Enhanced containment of replication was observed in monocyte-derived macrophages from a sub-group of BCG-vaccinated individuals (identified as ‘responders’). A stable and robust differential DNA methylation pattern in response to BCG could be observed in PBMCs isolated from the responders but not from the non-responders. Gene ontology analysis revealed that promoters with altered DNA methylation pattern were strongly enriched among genes belonging to immune pathways in responders, however no enrichments could be observed in the non-responders. Our findings suggest that BCG-induced epigenetic reprogramming of immune cell function can enhance anti-mycobacterial immunity. Understanding why BCG induces this responses in responders but not in nnon-responders could provide clues to improvement of TB vaccine efficacy.

2017-09-27 | GSE104287 | GEO

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