Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA121707 | ENA |
REPOSITORIES: ENA
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Project description:The success of many pathogens relies on their ability to circumvent the innate and adaptive immune defenses. How bacterial pathogens subvert host responses is not clear. Cholesterol-dependent cytolysins (CDCs) represent an expansive family of homologous pore-forming toxins produced by more than 20 Gram-positive bacterial species. Here we show that listeriolysin O (LLO), a prototype CDC produced by Listeria monocytogenes, inhibits antigen receptor-induced T cell proliferation. In vivo proliferation of OT II T cells was highly diminished in the presence of wild type but not the LLO-deficient bacteria. T cells pre-exposed to LLO ex vivo were also impaired in proliferation upon TCR activation in vivo and in vitro. Our results suggest that LLO-induced T cell unresponsiveness is due to the sub-threshold activation of T cells via the induction of a calcium-NFAT dependent transcriptional program that drives the expression of negative regulators of TCR signaling. Keywords: Listerilysin O, Ionomycin, 3 hours stimulation
2010-06-29 | GSE19337 | GEO
Project description:The success of many pathogens relies on their ability to circumvent the innate and adaptive immune defenses. How bacterial pathogens subvert host responses is not clear. Cholesterol-dependent cytolysins (CDCs) represent an expansive family of homologous pore-forming toxins produced by more than 20 Gram-positive bacterial species. Here we show that listeriolysin O (LLO), a prototype CDC produced by Listeria monocytogenes, inhibits antigen receptor-induced T cell proliferation. In vivo proliferation of OT II T cells was highly diminished in the presence of wild type but not the LLO-deficient bacteria. T cells pre-exposed to LLO ex vivo were also impaired in proliferation upon TCR activation in vivo and in vitro. Our results suggest that LLO-induced T cell unresponsiveness is due to the sub-threshold activation of T cells via the induction of a calcium-NFAT dependent transcriptional program that drives the expression of negative regulators of TCR signaling. Keywords: Listerilysin O, Ionomycin, 3 hours stimulation Pooled primary CD4+ T cells isolated from spleen and mesenteric lymph nodes were incubated in either control (Ctrl) medium or medium containing 0.25 ug/ml listeriolysin O (LLO) or 1 uM Ionomycin (Iono) for 3 hours. Thereafter, cells were washed and RNA was prepared.
2010-07-29 | E-GEOD-19337 | biostudies-arrayexpress
Project description:Upon infection, pathogens reprogram host gene expression. In eukaryotic cells, genetic reprogramming is induced by the concerted activation/repression of transcription factors and various histone modifications that control DNA accessibility in chromatin. We report here that the bacterial pathogen, Listeria monocytogenes, induces a dramatic dephosphorylation of histone H3 as well as a deacetylation of histone H4 during early phases of infection. This effect is mediated by the major listerial toxin listeriolysin (LLO), in a pore forming independent manner. Strikingly, a similar effect is also observed with other toxins of the same family, such as Clostridium perfringens perfringolysin (PFO) and Streptococcus pneumoniae pneumolysin (PLY). The decreased levels of histone modifications correlate with a reduced transcriptional activity of a subset of host genes, including key immunity genes. Thus, manipulation of the epigenetic information emerges here as an unsuspected function shared by several bacterial toxins, highlighting a common strategy used by intracellular and extracellular pathogens to modulate the host response early during infection.
2008-04-01 | E-MEXP-1078 | biostudies-arrayexpress
Project description:Mitochondrial function adapts to cellular demands and is affected by the ability of the organelle to undergo fusion and fission in response to physiological and non-physiological cues. We previously showed that infection with the human bacterial pathogen Listeria monocytogenes elicits transient mitochondrial fission and a drop in mitochondrial -dependent energy production through a mechanism requiring the bacterial pore-forming toxin listeriolysin O (LLO). Here, we performed quantitative mitochondrial proteomics to search for host factors involved in L. monocytogenes-induced mitochondrial fission. We found that Mic10, a critical component of the mitochondrial contact site and cristae organizing system (MICOS) complex, is significantly enriched in mitochondria isolated from cells infected with wild-type but not with LLO-deficient L. monocytogenes. Increased mitochondrial Mic10 levels did not correlate with upregulated transcription, suggesting a post-transcriptional regulation. We showed that Mic10 is necessary for L. monocytogenes-induced mitochondrial network fragmentation, and that it contributes to L. monocytogenes cellular infection independently of MICOS proteins Mic13, Mic26 and Mic27. Together, L. monocytogenes infection allowed us to uncover a role for Mic10 in mitochondrial fission.
2020-02-17 | PXD014667 | Pride
Project description:The formation of Listeria monocytogenes biofilms contributes to persistent contamination in food processing facilities. A microarray comparison of L. monocytogenes between the transcriptome of the strong biofilm forming strain (Bfms) Scott A and the weak biofilm forming (Bfmw) strain F2365 was conducted to identify genes potentially involved in biofilm formation. Among 951 genes with significant difference in expression between the two strains, a GntR-family response regulator encoding gene (LMOf2365_0414), designated lbrA, was found to be highly expressed in Scott A relative to F2365. A Scott A lbrA-deletion mutant, designated AW3, formed biofilm to a much lesser extent as compared to the parent strain by a rapid attachment assay and scanning electron microscopy. Complementation with lbrA from Scott A restored the Bfms phenotype in the AW3 derivative. A second microarray assessment using the lbrA deletion mutant AW3 and the wild type Scott A revealed a total of 304 genes with expression significantly different between the two strains, indicating the potential regulatory role of LbrA in L. monocytogenes. A cloned copy of Scott A lbrA was unable to confer enhanced biofilm forming potential in F2365, suggesting that additional factors contributed to weak biofilm formation by F2365. Findings from the study may lead to new strategies to modulate biofilm formation. Two comparisons were performed between 1) strong biofilm former Listeria monocytogenes strain ScottA versus weak biofilm former Listeria monocytogenes strain F2365; 2) Listeria monocytogenes ScottA LbrA deletion mutant strain versus Listeria monocytogenes ScottA. Four replicates were loaded for the first comparison and two replicates were loaded for the second comparison.
2012-09-06 | E-GEOD-40598 | biostudies-arrayexpress
Project description:Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria induce transcriptional changes, in order to modify the set of proteins synthetized by the host cell, or target pre-existing proteins by modulating their post-translational modifications or by triggering their degradation. Protein levels variations in host cells during infection integrates both transcriptional and post-transcriptional regulations induced by pathogens. Here, we focused on host proteome alterations induced by the bacterial pathogen Listeria monocytogenes, and more specifically the Listeria toxin Listeriolysin O (LLO). In order to characterize host proteome alterations induced by LLO, we performed a shotgun proteomics analysis on HeLa cells treated or not with the LLO toxin. To this end, we used SILAC labelling (stable isotope labelling by amino acids in cell culture) to compared in a quantitative manner the protein content from two differentially treated cell populations: one control population and one population incubated with a sublytic dose of LLO (3 nM). We decided to expose cells to LLO during only 20 min to limit protein level changes resulting from transcriptional changes. We performed two independent experiments (experiment #1 and experiment #2) with swapped SILAC labelling to rule out putative labelling-dependent effects. A total of 2009 and 1684 proteins was quantified in each independent experiment, respectively, and 1360 proteins were quantified in both experiments. Among these 1360 proteins, we identified a total of 91 proteins for which protein levels were consistently decreased in cells treated with LLO (i.e. with a log2 control/LLO ratio >0.5 in both experiments). To assess whether the host proteasome was involved in the decrease of these 91 proteins, we repeated our proteomics analysis on SILAC-labelled HeLa cells pre-treated with proteasome inhibitors before exposure to LLO. Two independent experiments were similarly performed with swapped SILAC labelling (experiment #3 and experiment #4). Interestingly, we observed that the vast majority of host proteins identified as strongly downregulated in response to LLO also displayed significant decreased levels in the presence of proteasome inhibitors, indicating that the majority of observed decreases in host protein levels induced by LLO are not due to proteasome-mediated degradation. In follow-up experiments, we identified that LLO decreases in particular the protein level of two E2 ubiquitin enzymes, UBE2K and UBE2N, leading to major changes in the host ubiquitylome. This toxin-induced proteome remodeling involves post-transcriptional regulations, as no modification in the transcription levels of the corresponding genes was observed. These decreases in host protein levels were observed in different epithelial cell lines but not in macrophages. In addition, we could show that Perfringolysin O, another bacterial pore-forming toxin similar to LLO, also induces host proteome changes. Taken together, our data show that different bacterial pore-forming toxins induce deep proteome remodeling, that may impair host epithelial cell functions.
2018-11-07 | PXD006900 | Pride
Project description:Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria induce transcriptional changes, in order to modify the set of proteins synthetized by the host cell, or target pre-existing proteins by modulating their post-translational modifications or by triggering their degradation. Protein levels variations in host cells during infection integrates both transcriptional and post-transcriptional regulations induced by pathogens. Here, we focused on host proteome alterations induced by the bacterial pathogen Listeria monocytogenes, and more specifically the Listeria toxin Listeriolysin O (LLO). In order to characterize host proteome alterations induced by LLO, we performed a shotgun proteomics analysis on HeLa cells treated or not with the LLO toxin. To this end, we used SILAC labelling (stable isotope labelling by amino acids in cell culture) to compared in a quantitative manner the protein content from two differentially treated cell populations: one control population and one population incubated with a sublytic dose of LLO (3 nM). We decided to expose cells to LLO during only 20 min to limit protein level changes resulting from transcriptional changes. We performed two independent experiments (experiment #1 and experiment #2) with swapped SILAC labelling to rule out putative labelling-dependent effects. A total of 2009 and 2577 proteins was quantified in each independent experiment, respectively, and 1834 proteins were quantified in both experiments. Among these 1834 proteins, we identified a total of 151 proteins for which protein levels were consistently decreased in cells treated with LLO (i.e. with a log2 control/LLO ratio >0.5 in both experiments). To assess whether the host proteasome was involved in the decrease of these 151 proteins, we repeated our proteomics analysis on SILAC-labelled HeLa cells pre-treated with proteasome inhibitors before exposure to LLO. Two independent experiments were similarly performed with swapped SILAC labelling (experiment #3 and experiment #4). Interestingly, we observed that the vast majority of host proteins identified as strongly downregulated in response to LLO also displayed significant decreased levels in the presence of proteasome inhibitors, indicating that the majority of observed decreases in host protein levels induced by LLO are not due to proteasome-mediated degradation. In follow-up experiments, we validated that LLO decreases in particular the protein level of two E2 ubiquitin enzymes, UBE2K and UBE2N, leading to major changes in the host ubiquitylome. This toxin-induced proteome remodeling involves post-transcriptional regulations, as no modification in the transcription levels of the corresponding genes was observed. These decreases in host protein levels were observed in different epithelial cell lines but not in macrophages. In addition, we could show that Perfringolysin O, another bacterial pore-forming toxin similar to LLO, also induces host proteome changes. Taken together, our data show that different bacterial pore-forming toxins induce deep proteome remodeling, that may impair host epithelial cell functions.
2018-11-07 | PXD006996 | Pride
Project description:This study will evaluate the safety and tolerability of a personalized live, attenuated, double-deleted Listeria monocytogenes (pLADD) treatment in adults with metastatic colorectal cancer.
| 2247134 | ecrin-mdr-crc
Project description:To characterize the molecular basis of cytotoxicity of different Pseudomonas species and strains, we analyzed the protein content of secretomes of three P. chlororaphis strains (CIP63, CIP75 and the reference strain PA23) and of six P. entomophila strains (L48 WT, or deleted for various virulence factors: the global activator GacA, the pore-forming toxin Mnl, the pore-forming toxin ExlA, and double mutants for these genes).
2022-07-25 | PXD029397 | Pride
Project description:Bacterial pathogens use various strategies to interfere with host cell functions. Among these strategies, bacteria induce transcriptional changes, in order to modify the set of proteins synthetized by the host cell, or target pre-existing proteins by modulating their post-translational modifications or by triggering their degradation. Protein levels variations in host cells during infection integrates both transcriptional and post-transcriptional regulations induced by pathogens. Here, we focused on host proteome alterations induced by the bacterial pathogen Listeria monocytogenes, and more specifically the Listeria toxin Listeriolysin O (LLO). In order to characterize host proteome alterations induced by LLO, we performed a shotgun proteomics analysis on HeLa cells treated or not with the LLO toxin. To this end, in a first analysis we used SILAC labelling (stable isotope labelling by amino acids in cell culture) to compare in a quantitative manner the protein content from two differentially treated cell populations: one control population and one population incubated with a sublytic dose of LLO (3 nM). We decided to expose cells to LLO during only 20 min to limit protein level changes resulting from transcriptional changes. We performed two independent experiments (experiment #1 and experiment #2) with swapped SILAC labelling to rule out putative labelling-dependent effects. A total of 2,009 and 2,577 proteins was quantified in each independent experiment, respectively, and 1,834 proteins were quantified in both experiments. Among these 1834 proteins, we identified a total of 151 proteins for which protein levels were consistently decreased in cells treated with LLO (i.e. with a log2 control/LLO ratio >0.5 in both experiments). In addition to this preliminary study, we carried out a second experiment using label-free quantitative shotgun proteomics to compare protein abundance in cells treated or not with LLO. Four independent biological replicates were included in this second screen in order to perform a robust statistical analyses of downregulated proteins. Among the 2,973 proteins that were quantified in all independent replicates, we identified a total of 149 proteins (5.0 %) for which protein levels were significantly decreased in cells treated with LLO. In contrast to these decreases, only 16 proteins (0.5 %) showed significant increased levels in LLO-treated cells. This result confirmed that LLO remodels the cell proteome mainly by decreasing the level of host targets. To assess whether the host proteasome was involved in the decrease of these 149 proteins, we repeated our label-free proteomics analysis on HeLa cells pre-treated with proteasome inhibitors before exposure to LLO. Interestingly, we observed that the vast majority (i.e. 83%) of host proteins identified as strongly downregulated in response to LLO also displayed significant decreased levels in the presence of proteasome inhibitors, indicating that the majority of observed decreases in host protein levels induced by LLO are not due to proteasome-mediated degradation. In follow-up experiments, we validated that LLO decreases in particular the protein level of two E2 ubiquitin enzymes, UBE2K and UBE2N, leading to major changes in the host ubiquitylome. This toxin-induced proteome remodeling involves post-transcriptional regulations, as no modification in the transcription levels of the corresponding genes was observed. These decreases in host protein levels were observed in different epithelial cell lines but not in macrophages. In addition, we could show that Perfringolysin O, another bacterial pore-forming toxin similar to LLO, also induces host proteome changes. Taken together, our data show that different bacterial pore-forming toxins induce deep proteome remodeling, that may impair host epithelial cell functions.
2018-05-17 | PXD009339 | Pride