Genome-wide gene expression changes in peripheral granulocytes and monocytes from TB patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE126614 | GEO | 2021/11/05
REPOSITORIES: GEO
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Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection. New Zealand White rabbits were infected with Mtb HN878 at 3.2log10 (on day 0). Lung tissue from Mtb-infected rabbits were isolated at Day0, 2, 4 and 16 weeks post infection and used for total RNA extraction.
2011-12-07 | E-GEOD-33094 | biostudies-arrayexpress
Project description:Mycobacterium tuberculosis (Mtb) has developed specialized mechanisms to parasitize its host cell, the macrophage. These mechanisms allow it to overcome killing by oxidative burst and persist in the wake of an inflammatory response. Mtb infection in the majority of those exposed is controlled in an asymptomatic form referred to as latent tuberculosis infection (LTBI). HIV is a well-known catalyst of reactivation of LTBI to active TB infection (ATB). Through the use of nonhuman primates (NHPs) co-infected with Mtb and Simian Immunodeficiency Virus (Mtb/SIV), we are able to simulate human progression of TB/AIDS comorbidity. The advantage of NHP models is that they recapitulate the breadth of human TB outcomes, including immune control of infection, and loss of this control due to SIV co-infection. Using macaques infected with Mtb or Mtb/SIV and with different clinical outcomes we attempted to identify signatures between those that progress to active infection after SIV challenge (reactivators) and those that control the infection (non-reactivators).
2022-09-23 | GSE213850 | GEO
Project description:Every year, tuberculosis kills nearly 1.8 million people through out the world. Though outcome of M. tuberculosis infection into active disease is determined by the host and bacterial factors, a strong host immune response controls the growth of the bacilli effectively. However, in a host with suboptimal immune response, the bacilli grows and mounts active disease. Activation of immune response following M. tuberculosis infection affects the expression of many host genes that are involved in the production of immune system molecules such as cytokines, chemokines, surface receptors and transcriptional regulators that manifest in the change of subsequent cellular events, including activation, maturation, chemotaxis and proliferation of effector cells. However, the specific nature of the host-pathogen interactions and the outcome of Mtb infection are not fully understood. In this study, we have analysed the systematic changes in the global host gene expression profile in the lungs of Mtb infected rabbits at various stages of infection. Mtb infected rabbit lung tissues were isolated at T=0,2, 4 and 16 weeks post-infection. Lung bacterial load, histologic changes and host and bacterial gene expression were determined for each timepoint and compared . Our data suggests a strong correlation between the significant changes in the global transcriptome of infected rabbits and the progression of Mtb infection into a chronic, cavitary TB disease. The microarray experiments involves comparison of: 1) Changes in rabbit gene expression between Mtb-HN878 infected and uninfected animals at 2,4 and 16 weeks post infection.
2011-12-07 | GSE33094 | GEO
Project description:Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
2019-12-10 | GSE141679 | GEO
Project description:Human infection with Mycobacterium tuberculosis results in a continuum of ill-defined, clinical manifestations with stable latent M. tuberculosis infection (LTBI) and severe active disease at the ends. Identifying different states of infection is of importance to tuberculosis (TB) control since risk of developing active disease varies among different asymptomatic states while infectiousness varies among patients with different bacterial burden. We investigated changes in proteome-scale antibody responses during disease progression in a non-human primate model of tuberculosis. We probed M. tuberculosis proteome microarrays with serial sera collected from three infection-outcome groups (active, reactivation, and latent). We found that each infection outcome is associated with characteristic changes in the antibody levels and number of antigenic targets, which suggested an association between antibody responses and bacillary burden. Additional proteome-scale serological profiling of > 400 human TB suspects established that antibody responses are positively associated with bacterial load. Thus tuberculosis-specific antibody levels and number of antigenic targets increases with disease progression.
2012-07-06 | GSE30722 | GEO
Project description:Even though recent reports estimate a reduction in the spread and contraction of Tuberculosis (TB), 30 % of the world population are currently being latently infected by Mycobacterium tuberculosis (Mtb). This latent infection can at any time develop into active disease. Biomarkers to monitor this process as well as biomarkers for disease susceptibility and TB diagnosis is urgently needed in order to facilitate a more drastic decrease in the spread of Mtb and better care for TB patients. Our understanding of biology combined with evolving technical advances in high-throughput techniques, led us to investigate the possibility of additional role players (epigenetics and proteomics) in the quest to (a) understand the biology of TB host response and (b) search for biomarkers in TB diagnostics and –susceptibility. We engaged in a pilot study, using a relatively small sample set to interrogate the DNA methylome, transcriptome and proteome in monocytes and granulocytes of TB patients and healthy latently infected participants. The observations in this study provide a first glimpse at the level- and sources of diversity in the epigenome and proteome amongst TB patients and latently infected controls despite limitations due to small sample size. Functionally the differences between the disease phenotypes observed in the different platforms were congruent and suggest regulation of function not only at the transcriptional level, but also by DNA methylation and microRNA. We conclude that the current data support the notion to develop a large scale study of especially the DNA methylome while care should be taken in the study design to account for variation based on gender, age and cell type.
2015-08-26 | PXD001960 | Pride
Project description:Human infection with Mycobacterium tuberculosis results in a continuum of ill-defined, clinical manifestations with stable latent M. tuberculosis infection (LTBI) and severe active disease at the ends. Identifying different states of infection is of importance to tuberculosis (TB) control since risk of developing active disease varies among different asymptomatic states while infectiousness varies among patients with different bacterial burden. We investigated changes in proteome-scale antibody responses during disease progression in a non-human primate model of tuberculosis. We probed M. tuberculosis proteome microarrays with serial sera collected from three infection-outcome groups (active, reactivation, and latent). We found that each infection outcome is associated with characteristic changes in the antibody levels and number of antigenic targets, which suggested an association between antibody responses and bacillary burden. Additional proteome-scale serological profiling of > 400 human TB suspects established that antibody responses are positively associated with bacterial load. Thus tuberculosis-specific antibody levels and number of antigenic targets increases with disease progression. Serum samples collected from adult patients with suspected tuberculosis during a multi-site study was used to probe whole proteome microarrays. Subject recruitment was conducted under uniform protocols approved by the institutional ethics committee at each site. Final diagnosis of active TB was based on positive M. tuberculosis culture results. The active TB patients were further subdivided into smear-positive and negative disease based on results of Ziehl-Neelsen staining of sputum smears for acid fast bacilli. Active TB was excluded as a diagnosis (Non-TB Disease [NTBD] patients) based on having negative M. tuberculosis culture and smear results and on having an alternate diagnosis. All subjects were presumably negative for HIV infection given the very low incidence of HIV infection in the study sites. Sera from 169 TB and 242 NTBD patients were selected for microarray probing. The control sera (n = 14) which was used to generate negative control distribution for each protein were negative to latent M. tuberculosis infection, as indicated by negative results to tuberculin skin test.
2012-07-05 | E-GEOD-30722 | biostudies-arrayexpress
Project description:Treatment of healthy donors with G-CSF and dexamethasone, results in sufficient number of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes as compared to control ones. Keywords: mobilized granulocytes, G-CSF/dexamethasone treated granulocytes
2009-09-09 | GSE12841 | GEO
Project description:Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the activities of multiple leukocyte subsets, yet the roles of the different innate effector cells during tuberculosis (TB) are incompletely understood. Here we show a role for eosinophils in host resistance to Mtb infection. In humans, eosinophils are found in resected human TB lung lesions and autopsy granulomas. Eosinophils are also found in granulomas in zebrafish, mice, and non-human primates, where they are functionally activated and degranulate. Transcriptional profiling of lung tissue after Mtb infection of mice, that selectively lack eosinophils, revealed changes in neuronal associated pathways. Importantly, employing several independent models of eosinophil deficiency in mice, we demonstrate that eosinophils are required for optimal pulmonary bacterial control and host survival after Mtb infection. Collectively, our findings establish an unexpected role for eosinophils, granulocytes typically associated with type II inflammation, in host resistance against Mtb, a major human bacterial pathogen.
2021-08-01 | GSE165871 | GEO
Project description:Treatment of healthy donors with G-CSF and dexamethasone, results in sufficient number of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes as compared to control ones. Keywords: mobilized granulocytes, G-CSF/dexamethasone treated granulocytes Granulocytes were isolated from three individuals before (control situation) and 18 hours after treatment with G-CSF&dexamethasone; part of the control cells was cultured overnight in HBSS medium with or without addition of G-CSF and dexamethasone. Total RNA from each experimental condition was compared to pooled RNA of control granulocytes.
2010-04-03 | E-GEOD-12841 | biostudies-arrayexpress