Caenorhabditis elegans
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ABSTRACT:
PROVIDER: PRJNA176153 | ENA |
REPOSITORIES: ENA
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Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response. In C. elegans, three mutant strains(genotypes used: N2 (wild-type), ogt-1 (ok1474), oga-1 (ok1207), and pmk-1 (km25)) were treated with the human pathogen S. aureus (SA) or P. aeruginosa(PA) and OP50 (E. coli control) with three biological replications.
2015-05-01 | E-GEOD-53732 | biostudies-arrayexpress
Project description:Traditional treatments for bacterial infection have focused upon directly inhibiting growth of the pathogen. However, an equally important determinant of infection outcome is the host defense response. We previously performed a high-throughput chemical screen to identify small molecules that rescued the nematode Caenorhabditis elegans from infection by Pseudomonas aeruginosa. Over 20 of the hits stimulated host defense gene expression. During in-depth studies of five such molecules using microarray analysis, bioinformatic clustering, and RNAi knockdown of candidate gene targets, we identified PMK-1/p38 MAPK and SKN-1/Nrf2 as two key pathways modulated by these hits. Interestingly, the molecules studied did not depend on a single pathway for ameliorating P. aeruginosa pathogenesis in liquid-based assay, but did rely on the PMK-1/p38 MAPK pathway during a colonization-based infection assay on agar. A subset of these molecules was also protective against Enterococcus faecalis and Staphylococcus aureus. In general, the compounds showed little toxicity against mammalian cells or worms, consistent with their identification in a phenotypic, high-content screen. These molecules possess significant potential for use as tools to study innate immune processes
2020-09-19 | GSE137516 | GEO
Project description:Discriminating pathogenic bacteria from energy-harvesting commensals is key to host immunity. Using mutants defective in the enzymes of O-linked N-acetylglucosamine (O-GlcNAc) cycling, we examined the role of this nutrient-sensing pathway in the Caenorhabidits elegans innate immune response. Using whole genome transcriptional profiling, O-GlcNAc cycling mutants exhibited deregulation of unique stress- and immune-responsive genes as well as genes shared with the p38 MAPK/PMK-1 pathway. Moreover, genetic analysis showed that deletion of O-GlcNAc transferase (ogt-1) yielded animals hypersensitive to the human pathogen S. aureus but not to P. aeruginosa. Genetic interaction studies further revealed that nutrient-responsive OGT-1 acts through the conserved ß-catenin (BAR-1) pathway and in concert with p38 MAPK/PMK-1 to modulate the immune response to S. aureus. The participation of the nutrient sensor O-GlcNAc transferase in an immunity module conserved from C. elegans to humans reveals an unexplored nexus between nutrient availability and a pathogen-specific immune response.
2015-05-01 | GSE53732 | GEO
Project description:PMK-1 is involved in the heat stress response of C. elegans, translocates to the nucleus upon heat exposure and influences the expression of chaperone genes, proteasomal subunits and protein-biosynthesis related genes. Differential Gene expression of WT and pmk-1 deletion mutant (KU25) after 5 hours at 35°C
2012-11-05 | E-GEOD-41205 | biostudies-arrayexpress
Project description:PMK-1 is involved in the heat stress response of C. elegans, translocates to the nucleus upon heat exposure and influences the expression of chaperone genes, proteasomal subunits and protein-biosynthesis related genes.
2012-11-05 | GSE41205 | GEO
Project description:Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. Here, we study the adverse effects of GO and amino-functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA-Seq data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK-1, which is a well-established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk-1 mutants show reduced tissue-functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk-1 mutants, and the innate immune response is considerably less pronounced. Our work establishes the enhanced biocompatibility of amino-functionalized GO in a whole-organism, emphasizing its potential as biomedical nanomaterial.
2022-05-10 | GSE131070 | GEO
Project description:Cisplatin kills proliferating cells via DNA damage but also has profound effects on post-mitotic cells in tumors, kidneys, and neurons. However, the effects of cisplatin on post-mitotic cells are still poorly understood. Among model systems, C. elegans adults are unique in having completely post-mitotic somatic tissues. The p38 MAPK pathway controls ROS detoxification via SKN-1/NRF and immune responses via ATF-7/ATF2. We show that p38 MAPK pathway mutants are sensitive to cisplatin, but while cisplatin exposure increases ROS levels, skn-1 mutants are resistant. Cisplatin exposure leads to phosphorylation of PMK-1/MAPK and ATF-7 and the IRE-1/TRF-1 signaling module functions upstream of the p38 MAPK pathway to activate signaling. We identify the response proteins whose increased abundance depends on IRE-1/p38 MAPK activity as well as cisplatin exposure. Four of these proteins are necessary for protection from cisplatin toxicity, which is characterized by necrotic death. We conclude that the p38 MAPK pathway-driven proteins are crucial for adult cisplatin resilience.
2023-04-26 | PXD033377 | Pride
Project description:Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. We found that losing one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, results in hypersusceptibility to both P. aeruginosa and ToxA. We determined that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 PMK-1 MAPK signaling. Here we present the microarray data that was used to determine that (1) nipi-3 regulates immune gene expression and that (2) nipi-3 and pmk-1 regulate non-overlapping gene sets consistent with them functioning in parallel. We used microarray analysis to identify the genes regulated by nipi-3 and pmk-1 at the L4 stage.
2016-09-18 | GSE87052 | GEO
Project description:Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development, also de-represses the p38 MAPK PMK-1 pathway in the intestine to promote immune effector transcription, increased clearance of an intestinal pathogen and resistance to bacterial infection. These data reveal an unexpected connection between olfactory receptor development and innate immunity, and show that anti-pathogen defenses in the intestine are developmentally programmed.
2020-03-04 | GSE130959 | GEO