EHEC Tir regulate the expression of genes in primary macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE112418 | GEO | 2018/03/29
REPOSITORIES: GEO
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:EHEC Tir regulate the expression of genes in primary macrophages
| PRJNA445962 | ENA
Project description:Fimbriae are important virulence traits that promote bacterial adhernece to surfaces. Here, we assessed whether fimbriae modulate gene expression using microarrays. We used microarrays to compare gene expression in wild-type of fimbrial deletion strains of EHEC
2024-06-07 | GSE100200 | GEO
Project description:Toll/interleukin-1 receptor (TIR) domains across different life kingdoms possess NADase activities and produce distinct small molecules including phosphoribosyl adenosine monophosphate/diphosphate (pRib-AMP/ADP) and two cyclic ADPR (cADPR) isomers 2’cADPR and 3’cADPR. Plant intracellular nucleotide-binding leucine-rich repeat (NLR) receptors with an N-terminal TIR domain sense pathogen effectors to initiate immune signaling and rely on downstream helper NLRs to execute immune function. Lipase-like proteins EDS1 and PAD4 transduce immune signals from sensor TIR-NLRs to a helper NLR called ADR1. We report the structure and function of Arabidopsis EDS1-PAD4-ADR1 (EPA) heterotrimer in complex with pRib-AMP/ADP activated by plant or bacterial TIR signaling. Bacterial TIRs that produce 2’cADPR, but not 3’cADPR, induce EPA complex formation and activate EPA signaling using pRib-AMP as the signaling molecule. 2’cADPR is hydrolyzed into pRib-AMP in vivo. 2’cADPR, but not 3’cADPR, induces EPA-dependent defense genes expression. Our findings shed light on the activation mechanisms of ADR1 by EDS1-PAD4 involving two structurally-related molecules with 2’cADPR likely being the storage form of the unstable signaling molecule pRib-AMP, as well as cross-talks between plant and bacterial TIR immune signaling.
2025-01-29 | GSE277725 | GEO
Project description:Intracellular signaling regulators are concentrated into membrane-free, higher-ordered protein assemblies to initiate protective responses during stress — a process known as phase transition. Here, we show that a phase transition of the C. elegans Toll/interleukin-1 receptor domain protein (TIR-1), a homolog of the mammalian sterile alpha and TIR motif-containing 1 (SARM1), primes host immune defenses when dietary sterols are limited to handle subsequent bacterial infection. TIR-1/SARM1 is an upstream component of the p38 PMK-1 pathway in intestinal cells, an innate immune defense and stress response pathway in metazoans. Under conditions of low cholesterol availability, multimerization and precipitation of TIR-1/SARM1 potentiates the intrinsic NAD+ glycohydrolase activity of this protein complex, increases p38 PMK-1 phosphorylation, and promotes pathogen clearance from the intestine. Dietary cholesterol is required for C. elegans to survive infection with pathogenic bacteria and to support development, fecundity, and lifespan. Thus, activation of the p38 PMK-1 pathway in sterol-deficient animals is an adaptive response that allows a metazoan host to anticipate environmental threats under conditions of essential metabolite scarcity.
2022-03-18 | GSE178572 | GEO
Project description:Bacterial pathogens must be able to both recognize suitable niches within the host for colonization and successfully compete with commensal flora for nutrients in order to establish infection. Ethanolamine (EA) is a major component of mammalian and bacterial membranes and may be used by pathogens as a carbon and/or nitrogen source in the gastrointestinal tract. We examined how EA influences gene expression in the human pathogen enterohemorrhagic Escherichia coli O157:H7 (EHEC). Our results indicate EA is not only important for nitrogen metabolism, but that EA is used in cell-to-cell signaling to activate virulence gene expression. Genes encoding for the global regulatory proteins QseC, QseE, and QseA, as well as for attaching and effacement (AE) lesion formation and Shiga toxin are differentially regulated when EHEC is grown with micromolar concentrations of EA. We also constructed a deletion of eutR that encodes the regulator of the eut (EA utilization) operon and examined virulence gene expression. These results suggest that EutR is important in regulating gene expression in response to EA, but that EA signaling does not occur solely through EutR. This is the first report linking EA to cell-to-cell signaling and pathogenesis.
2012-06-18 | GSE34046 | GEO
Project description:Programmed cell suicide of infected bacteria, known as abortive infection (Abi), serves as a central immune defense strategy to prevent the spread of bacteriophage viruses and other invasive genetic elements across a population. Many Abi systems utilize bespoke cyclic nucleotide immune messengers generated upon infection to rapidly mobilize cognate death effectors. Here, we identify a large family of bacteriophage nucleotidyltransferases (NTases) which synthesize competitor cyclic dinucleotide (CDN) ligands and inhibit NAD-depleting TIR effectors activated through a linked STING CDN sensor domain (TIR-STING). Through a functional screen of NTase-adjacent phage genes, we uncover candidate inhibitors of host TIR-STING suicide signaling. Among these, we demonstrate that a virus MazG-like nucleotide pyrophosphatase, Atd1, depletes the starvation alarmone (p)ppGpp, revealing a role for the alarmone-activated host toxin MazF as a key executioner of TIR-driven abortive infection. Phage NTases and counter-defenses like Atd1 preserve host viability to ensure virus propagation, and may be exploited as tools to modulate TIR and STING immune responses.
2023-03-27 | GSE222071 | GEO
Project description:Adherence of pathogenic Escherichia coli strains to intestinal epithelia is essential for infection. For enterohemorrhagic E. coli (EHEC) serotype O157:H7, we have previously demonstrated that multiple factors govern this pathogen’s adherence to HeLa cells (39). One of these factors is CadA, a lysine decarboxylase, and this protein has been proposed to negatively regulate virulence in several enteric pathogens. In the case of EHEC strains, CadA modulates expression of the intimin, an outer membrane adhesin involved in pathogenesis. Here, we experimentally inactivated cadA in O157:H7 strain 86-24 to investigate the role of this gene in EHEC adhesion to tissue culture monolayers, global gene expression patterns, and colonization of the infant rabbit intestine. As expected, the cadA mutant did not possess lysine decarboxylation activity and was hyper-adherent to tissue-culture cells. Adherence of the cadA mutant was nearly 2-fold greater than that of the wt and complementation of the cadA defect reduced adherence back to wt levels. Furthermore, the cadA mutant affected the expression of intimin protein. Disruption of the eae gene (encoding the intimin protein) in the cadA mutant significantly reduced its adherence to tissue-culture cells. However, adherence of the cadA eae double mutant was greater than that of an 86-24 eae mutant, suggesting that the enhanced adherence of the cadA mutant is not entirely attributable to enhanced expression of intimin in this background. Gene array analysis revealed that the cadA mutation significantly altered EHEC gene expression patterns; expression of 1332 genes was down-regulated and 132 genes up-regulated in the mutant compared to the wild type strain. Interestingly, the gene expression variation shows an EHEC-biased gene alteration including intergenic regions. Two putative adhesins: flagella and F9 fimbriae were up-regulated in the cadA mutant, suggestive of their association with adherence in absence of the Cad regulatory mechanism. Remarkably, in the infant rabbit model, the cadA mutant out-competed the wild type strain in the ileum but not in the cecum or mid-colon, raising the possibility that CadA negatively regulates EHEC pathogenicity in a tissue-specific fashion.
2008-09-18 | GSE11927 | GEO
Project description:Intracellular signaling regulators can be concentrated into membrane-free, higher-ordered protein assemblies to initiate protective responses during stress — a process known as phase transition. Here, we show that a phase transition of the Caenorhabditis elegans Toll/interleukin-1 receptor domain protein (TIR-1), an NAD+ glycohydrolase homologous to mammalian sterile alpha and TIR motif-containing 1 (SARM1), underlies p38 PMK-1 immune pathway activation in C. elegans intestinal epithelial cells. Through visualization of fluorescently labeled TIR-1/SARM1 protein, we demonstrate for the first time that physiologic stresses, both pathogen and non-pathogen, induce multimerization of TIR-1/SARM1 into visible puncta within intestinal epithelial cells. In vitro enzyme kinetic analyses revealed that, like mammalian SARM1, the NAD+ glycohydrolase activity of C. elegans TIR-1 is dramatically potentiated by protein oligomerization and a phase transition. Accordingly, C. elegans with genetic mutations that specifically block either multimerization or the NAD+ glycohydrolase activity of TIR-1/SARM1 fail to induce p38 PMK phosphorylation, are unable to increase immune effector expression, and are dramatically susceptible to bacterial infection. Finally, we demonstrate that low cholesterol stress causes TIR-1/SARM1 to oligomerize into puncta in intestinal epithelial cells and engages its NAD+ glycohydrolase activity, which increases p38 PMK-1 phosphorylation, and primes immune effector induction in a manner that leads to reduced pathogen accumulation in the intestine during a subsequent infection. These data reveal a new adaptive response that allows a metazoan host to anticipate pathogen threats during micronutrient deprivation, a time of relative susceptibility to infection. Thus, a phase transition of TIR-1/SARM1 as a prerequisite for its NAD+ glycohydrolase activity is strongly conserved across millions of years of evolution and is essential for diverse physiological processes in multiple cell types.
2021-12-16 | GSE190585 | GEO
Project description:Among the diseases caused by Toll-like receptor 4 (TLR4) abnormal activation by bacterial endotoxin, sepsis is the most dangerous one. The reprogramming of macrophages plays a crucial role in orchestrating the pathogenesis of sepsis. However, the precise mechanism underlying TLR4 activation in macrophages remained incompletely understood. Our studies revealed that upon lipopolysaccharide (LPS) stimulation, CREB-binding protein (CBP) was recruited to the TLR4 signalosome complex and resulted in pronounced acetylation in the TIR domains of TLR4, Myeloid differentiation factor 88 (MyD88) and MyD88 adapter-like (MAL), which significantly enhanced the activation of the NF-κB signaling pathway and polarization of M1 macrophages. In sepsis patients, significantly elevated TLR4-TIR acetylation was detected in CD16+ monocytes combined with elevated expression of M1 macrophage markers and production of pro-inflammatory cytokines. In contrast, histone deacetylase 1 (HDAC1) served as a key deacetylase in the deacetylation of the TIR domain complex. The inhibition of HDAC1 accelerated sepsis-associated syndromes, while the inhibition of CBP alleviated this process. Overall, our findings highlighted the crucial role of TIR domain complex acetylation in the regulation of inflammatory immune response and suggested that the reversible acetylation of the complex emerged as a promising therapeutic target for M1 macrophages during the progression of sepsis.
2024-08-01 | GSE268406 | GEO