Gene expression comparison between Mycobacterium tuberculosis infected monocytes from tuberculous and healthy elders
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE57736 | GEO | 2014/08/29
SECONDARY ACCESSION(S): PRJNA247977
REPOSITORIES: GEO
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Project description:Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected with M. tuberculosis monocytes from both, healthy elders (a tuberculosis susceptibility group) and elderly tuberculosis patients, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns of these genes regardless of whether they were obtained from younger or elder patients. Only one of the detected genes corresponded to a cytokine: IL-26, a member of the IL-10 cytokine family that we found downregulated in infected monocytes from tuberculosis patients. We have analyzed total RNA from Mycobacterium tuberculosis infected monocytes. We have isolated CD14+ cells (monocytes) from peripheral blood mononuclear cells by magnetic separation, and infected them for 4 days with 1 bacterium per monocyte. Blood donors were 7 elderly patients with pulmonary tuberculosis (average age: 83 years; sex: 3 men and 4 women) and 8 non-tuberculous volunteers (81 years, 6 men and 2 women).
2014-08-29 | E-GEOD-57736 | biostudies-arrayexpress
Project description:To assess the function of peripheral blood derived monocytes in patently infected filaria patients (either Wuchereria bancrofti, Mansonella perstans, or both), we investigated the cytokine production and gene expression profile of these cells in filaria infected patients and compared them with those from uninfected normal blood bank donors. Monocytes from infected individuals were studded with intracellular microfilarial antigens. In addition, Staphylococcus aureus Cowan I bacteria (SAC)/IFN γ activated monocytes from the infected individuals produced less IL 8, Exodus II, MIP 1a, MIP 1b, eotaxin, RANTES, IL 1a, and MIP 3b compared with normal patients. Microarray analysis of ex vivo isolated monocytes demonstrated that multiple genes involved in signal transduction, apoptosis, and adhesion were expressed to a greater degree in filaria infected patient monocytes compared with those of uninfected normal individuals. Eight months following treatment with a single dose of ivermectin/albendazole, monocytes of W. bancrofti infected individuals were capable of producing more IL 8, IL 1a, MIP 1a, and IL 10 in response to SAC/IFN γ compared with their pretreatment levels. Further, when monocyte global expression was compared before and after treatment of the W. bancrofti, there was a marked increase in mRNA expression of genes associated with protein metabolism, and in HSP most particularly, compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria infected patients are altered; however, this dysfunction can be reveresed to a degree following treatment with a single dose of ivermection/albendazole.
2008-06-12 | E-GEOD-2135 | biostudies-arrayexpress
Project description:Tuberculosis remains a major cause of death from an infectious disease worldwide, yet only 10% of people infected with Mycobacterium tuberculosis develop disease. Defining both necessary and sufficient immunologic determinants of protection remains a great scientific challenge. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify human potential candidate markers of host defense by studying gene expression profiles of macrophages, cells which, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene co-expression network analysis revealed an association between the cytokine, IL-32, and the vitamin D antimicrobial pathway in a network of IFN-γ and IL-15 induced ‘defense response’ genes. IL-32 was sufficient for induction of the vitamin D-dependent antimicrobial peptides, cathelicidin and DEFB4, and generation of antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. The IL-15 induced ‘defense response’ macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent vs. active tuberculosis or healthy controls, and a co-expression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15 induced gene network. Inferring that maintaining M. tuberculosis in a latent state and preventing transition to active disease represents host resistance, we believe these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis. Adherent peripheral blood monuclear cells were derived by Ficoll-Hypaque from the whole blood of four healthy donors. Cells adhered to tissue culture-treated plates for 2 h in 1% Fetal Bovine Serum (FBS) in RPMI. Cells were washed then stimulated with IL-10 (10ng/ml), IL-15 (10ng/ml) (R&D Systems), or IL-4 (1U/ml) in RPMI 1640 supplemented with 10% FBS at 37°C, 5% CO2. Cells were harvested at 6 h and 24 h after stimulation and monocytes purified by CD14 microbeads (Miltenyi Biotec) for a confirmed monocyte purity of at least 90%. RNA from purified monocytes extracted by Trizol and purified by Qiagen RNeasy Kit. RNA probe and microarray performed by UCLA Clinical Microarray Core using Ambion labeling kit and Affymetrix Human U133 Plus 2.0 array.
2014-08-20 | E-GEOD-59184 | biostudies-arrayexpress
Project description:Analysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 1] Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of mortality and morbidity worldwide, causing approximately 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL?12, IL?1 and TNF??, as well as IFN?? and CD4+ Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I interferon have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL?10 is known to inhibit the immune response to Mtb in murine models through the negative regulation of key pro-inflammatory cytokines and the subsequent Th1 response. We show here, using a combination of transcriptomic analysis, genetics and pharmacological inhibitors that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I interferon production. The TPL-2-ERK1/2 signalling pathway regulated production by macrophages of several cytokines important in the immune response to Mtb as well as regulating induction of a large number of additional genes, many in a type I IFN dependent manner. In the absence of TPL-2 in vivo, excess type I interferon promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I interferon may promote susceptibility to this important disease. Macrophages were derived from C57Bl/6 bone marrow, plated and infected with Mtb H37Rv (or not) in duplicate wells. Samples were then harvested for RNA at time 0 (uninfected only), 15m, 30m, 1hr, 3hr, 6hr and 24hr.
2013-09-05 | E-GEOD-47672 | biostudies-arrayexpress
Project description:To assess the function of peripheral blood derived monocytes in patently infected filaria patients (either Wuchereria bancrofti, Mansonella perstans, or both), we investigated the cytokine production and gene expression profile of these cells in filaria infected patients and compared them with those from uninfected normal blood bank donors. Monocytes from infected individuals were studded with intracellular microfilarial antigens. In addition, Staphylococcus aureus Cowan I bacteria (SAC)/IFN γ activated monocytes from the infected individuals produced less IL 8, Exodus II, MIP 1a, MIP 1b, eotaxin, RANTES, IL 1a, and MIP 3b compared with normal patients. Microarray analysis of ex vivo isolated monocytes demonstrated that multiple genes involved in signal transduction, apoptosis, and adhesion were expressed to a greater degree in filaria infected patient monocytes compared with those of uninfected normal individuals. Eight months following treatment with a single dose of ivermectin/albendazole, monocytes of W. bancrofti infected individuals were capable of producing more IL 8, IL 1a, MIP 1a, and IL 10 in response to SAC/IFN γ compared with their pretreatment levels. Further, when monocyte global expression was compared before and after treatment of the W. bancrofti, there was a marked increase in mRNA expression of genes associated with protein metabolism, and in HSP most particularly, compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria infected patients are altered; however, this dysfunction can be reveresed to a degree following treatment with a single dose of ivermection/albendazole. Keywords: other
2005-01-12 | GSE2135 | GEO
Project description:Analysis of Mtb infected murine macrophages derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNAR DKO mice [Set 2] Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of mortality and morbidity worldwide, causing approximately 1.4 million deaths per year. Key immune components for host protection during tuberculosis include the cytokines IL‐12, IL‐1 and TNF‐α, as well as IFN‐γ and CD4+ Th1 cells. However, immune factors determining whether individuals control infection or progress to active tuberculosis are incompletely understood. Excess amounts of type I interferon have been linked to exacerbated disease during tuberculosis in mouse models and to active disease in patients, suggesting tight regulation of this family of cytokines is critical to host resistance. In addition, the immunosuppressive cytokine IL‐10 is known to inhibit the immune response to Mtb in murine models through the negative regulation of key pro-inflammatory cytokines and the subsequent Th1 response. We show here, using a combination of transcriptomic analysis, genetics and pharmacological inhibitors that the TPL-2-ERK1/2 signaling pathway is important in mediating host resistance to tuberculosis through negative regulation of type I interferon production. The TPL-2-ERK1/2 signalling pathway regulated production by macrophages of several cytokines important in the immune response to Mtb as well as regulating induction of a large number of additional genes, many in a type I IFN dependent manner. In the absence of TPL-2 in vivo, excess type I interferon promoted IL-10 production and exacerbated disease. These findings describe an important regulatory mechanism for controlling tuberculosis and reveal mechanisms by which type I interferon may promote susceptibility to this important disease. Macrophages were derived from C57Bl/6 WT, TPL2KO, IFNARKO & TPL2IFNARKO bone marrow, plated and infected with Mtb H37Rv (or not) in triplicate wells. The indicated samples were also treated with 5ng/ml IFNgamma at the time of infection. Samples were then harvested for RNA at time 0, 1hr and 6hr. Please note that *Sample and *Medium control samples (e.g. '0hr TPL2-/-IFNabR-/- Sample' vs '0hr TPL2-/-IFNabR-/- Medium Control Sample') are the same sample group (i.e. uninfected) with one group being a repeat re-run of the other (indicated in the correponding SAMPLE description field).
2013-09-05 | E-GEOD-47673 | biostudies-arrayexpress
Project description:The cytokine IL-10 deactivates macrophages and has been shown to impair resistance to mycobacterial infection. We have infected transgenic mice overexpressing IL-10 under control of the macrophage-specific CD68 promoter (macIL-10tg mice) with Mycobacterium tuberculosis by aerosol and found increased bacterial loads in the lungs of macIL-10tg mice. To identify programs of genes regulated by IL-10 and associated with increased mycobacterial replication, genome-wide expression analysis was performed. Experiment Overall Design: Impact of IL-10 pulmonary gene expression in mouse M. tuberculosis infection
2009-01-17 | E-GEOD-14316 | biostudies-arrayexpress
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry. The proposed study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis coinfected with HIV and four head injury cases were used as controls. We have used 4X44K arrays from agilent platform. To validate our microarray results, we have done immunohistochemistry on 10 TBM+HIV cases and 10 control groups.
2012-12-31 | E-GEOD-29507 | biostudies-arrayexpress
Project description:The cytokine environment and cellular infiltrate during an inflammatory response may contain prognostic features that could guide therapy or predict disease outcome. Here we analyzed the transcriptional responses of human monocytes, macrophages, dendritic cells and neutrophils to stimulation by type 1 cytokines (IFN-g, IFN-b and IFN-l) type 2 cytokines (IL-4 and IL-13) and the immunoregulatory cytokine IL-10. This generated a myeloid cell cytokine specific response matrix to infer representation of myeloid cells and the cytokine environment they may encounter during infection and in tumors. Neutrophils were surprisingly responsive to type 1 and type 2 cytokine stimulation but did not respond to IL-10. We identified transcripts specific to IFN-b stimulation, whereas other IFN signature genes were upregulated by both IFN-g and IFN-b. When used to deconvolute blood profiles from tuberculosis patients, the IFN-b specific neutrophil signature was surprisingly reduced in TB patients with active disease whereas the shared response to IFN-g and IFN-b in neutrophils was increased. When applied to glioma patients, transcripts of neutrophils exposed to IL-4 or IL-13 and monocyte responses to IFN-g or IFN-b emerged as opposing predictors of survival in samples from patients with glioma. This approach may help delineate biological roles for myeloid cells in different cytokine environments during disease processes.
2020-02-21 | GSE145647 | GEO
Project description:The cytokine environment and cellular infiltrate during an inflammatory response may contain prognostic features that could guide therapy or predict disease outcome. Here we analyzed the transcriptional responses of human monocytes, macrophages, dendritic cells and neutrophils to stimulation by type 1 cytokines (IFN-g, IFN-b and IFN-l) type 2 cytokines (IL-4 and IL-13) and the immunoregulatory cytokine IL-10. This generated a myeloid cell cytokine specific response matrix to infer representation of myeloid cells and the cytokine environment they may encounter during infection and in tumors. Neutrophils were surprisingly responsive to type 1 and type 2 cytokine stimulation but did not respond to IL-10. We identified transcripts specific to IFN-b stimulation, whereas other IFN signature genes were upregulated by both IFN-g and IFN-b. When used to deconvolute blood profiles from tuberculosis patients, the IFN-b specific neutrophil signature was surprisingly reduced in TB patients with active disease whereas the shared response to IFN-g and IFN-b in neutrophils was increased. When applied to glioma patients, transcripts of neutrophils exposed to IL-4 or IL-13 and monocyte responses to IFN-g or IFN-b emerged as opposing predictors of survival in samples from patients with glioma. This approach may help delineate biological roles for myeloid cells in different cytokine environments during disease processes.
2019-10-01 | GSE131990 | GEO