Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse MH-S cell line with methylglyoxal induces apoptosis and immune response

ABSTRACT: Mycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles. Experiment Overall Design: MH-S cells (ATCC Number: CRL-2019), an alveolar macrophage cell line, was treated with 0.8 mM MG. At different time points after treatment (30 min, 4 h, and 8 h) the cells were harvested for total RNA preparation. As negative control the cells without treatment were included. RNA preparation was performed using Trizol method. Totally three independent experiments were performed, so that each time point consists of biological triplicates.

ORGANISM(S): Mus musculus

SUBMITTER: Helmy Rachman

PROVIDER: E-GEOD-3837 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.

Rachman Helmy H Kim Nayoung N Ulrichs Timo T Baumann Sven S Pradl Lydia L Nasser Eddine Ali A Bild Matthias M Rother Marion M Kuban Ralf-Jürgen RJ Lee Jong Seok JS Hurwitz Robert R Brinkmann Volker V Kosmiadi George A GA Kaufmann Stefan H E SH

PloS one 20061220

Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-alpha as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products (AGE) during mycobacterial infection of macrophages, leading to apoptosis and activation ...[more]

PMID: 17183656

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Project description:The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific innate immune responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be a deadly disease, only 5-10% of individuals infected with MTB develop active disease, and this inter-individual variation is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacterial pathogens, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. We found that although the gene expression changes were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB. RNA-seq of monocyte-derived macrophages isolated from 6 healthy European males at 4, 18, and 48 hours post-infection with the following 8 bacteria: Mycobacterium tuberculosis (MTB) H37Rv, Mycobacterium tuberculosis GC1237, MTB GC1237, bacillus Calmette-Guérin (BCG), Mycobacterium smegmatis, Yersinia pseudotuberculosis, Salmonella typhimurium, and Staphylococcus epidermidis. table-s1.txt is a tab-delimited text file that contains the batch-corrected log2 counts per million for each of the 156 samples, as well as the Ensembl gene ID and gene name. BCG = bacillus Calmette-Guérin GC = Mycobacterium tuberculosis GC1237 Rv = Mycobacterium tuberculosis (MTB) H37Rv Rv+ = heat-inactivated MTB H37Rv Salm = Salmonella typhimurium Smeg = Mycobacterium smegmatis Staph = Staphylococcus epidermidis Yers = Yersinia pseudotuberculosis

Project description:Tuberculosis results from an interaction between a chronically persistent pathogen counteracted by IFN-g-mediated immune responses. Modulation of IFN-g signaling could therefore constitute a major immune evasion mechanism for M. tuberculosis. SOCS1 plays a major role in the inhibition of IFN-g-mediated responses. We found that M. tuberculosis infection stimulates SOCS1 expression in mouse and human myeloid cells. Significantly higher levels of SOCS1 were induced after in vitro or in vivo infection with virulent M. tuberculosis-than with attenuated M. bovis BCG. Different innate and adaptive immune mechanisms participated in infection-induced SOCS1 expression. SOCS1 hampered M. tuberculosis clearance both in macrophages and during murine infection in vivo. On the other hand, SOCS1 protected the host from an infection-induced inflammation. Despite SOCS1 expression, mycobacteria-infected macrophages were not tolerant to IFN-g. Instead, an impaired IFN-g secretion by macrophages, associated to lower responses to IL-12, accounted for the increased mycobacterial intracellular growth in presence of SOCS1. SOCS1 attenuated the expression of the majority of genes modulated by infection of macrophages (6,1% of the transcriptome), indicating the relevance of the molecule in the outcome of infection with M. tuberculosis. We suggest that SOCS1 is expressed during M. tuberculosis infection to establish a successful chronic infection, and dampen inflammatory damage. Difference in genotype and TB infection comparison Relative gene expressions were determined by normalized intensity values. GeneSpring analysis was performed using the Treg transcriptome data with following comparisons: no GvHD d90 versus no GvHD d150, no GvHD d90 versus acute GvHD, no GvHD d150 versus chronic GvHD, acute GvHD versus chronic GvHD, acute GvHD versus GvHD d90 and chronic GvHD versus GvHD d150 (Figure 2). Cut-off was a transcript fold change of +2 or -2 in at least one comparison. Student´s t-test was used to identify significant expression changes.

Dataset Information

Transcription profiling of mouse MH-S cell line with methylglyoxal induces apoptosis and immune response

Publications

Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.

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