Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Released palmitic acid–mediated TLR4/NF-κB activation enhances the virulence of Bordetella pertussis MT28 lineage

ABSTRACT:

Whooping cough resurged globally despite the widespread vaccination. A macrolide-resistant (MR) lineage carrying the high-virulence ptxP3 allele, ptxP3 MR-MT28 (MT28), has imposed a substantial burden on pertussis epidemics, while the underlying factors driving its prevalence remain unclear. Thus, we performed an epidemiological surveillance and bacterial genomic, phenotypic, in vitro and in vivo pathogenicity analyses. We found MT28 lineage exhibits enhanced abilities of colonization and pro-inflammatory. Transcriptomic analysis revealed significant upregulation of key virulence genes (ptxA, fhaB, tcfA and bvgA), suggesting a molecular basis for its transmission and pathogenicity. Further, lipid-targeted metabolomics and liquid chromatography-mass spectrometry (LC-MS) identified B. pertussis-derived palmitic acid (PA) as a crucial pro-inflammatory mediator that promotes MT28 pathogenicity via the TLR4/NF-κB signaling pathway. These findings elucidate the mechanisms underlying the prevalence and increased pathogenicity of the MT28 lineage, and propose a novel pathogenic mechanism of B. pertussis involving PA-mediated activation of the TLR4/NF-κB inflammatory signaling pathway.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase

PROVIDER: MTBLS13545 | MetaboLights | 2025-12-21

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	a_MTBLS13545_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13545_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13545.txt	Txt

Items per page:

1 - 4 of 4

Similar Datasets

Palmitic acid-mediated TLR4/NF-κB activation drives the pathogenicity of hypervirulent Bordetella pertussis MT28 lineage

Project description:<p>Whooping cough resurged globally despite the widespread vaccination. A macrolide-resistant (MR) lineage carrying the high-virulence ptxP3 allele, ptxP3 MR-MT28 (MT28), has imposed a substantial burden on pertussis epidemics, while the underlying factors driving its prevalence remain unclear. Thus, we performed an epidemiological surveillance and bacterial genomic, phenotypic, in vitro and in vivo pathogenicity analyses. We found MT28 lineage exhibits enhanced abilities of colonization and pro-inflammatory. Transcriptomic analysis revealed significant upregulation of key virulence genes (ptxA, fhaB, tcfA and bvgA), suggesting a molecular basis for its transmission and pathogenicity. Further, lipid-targeted metabolomics and liquid chromatography-mass spectrometry (LC-MS) identified B. pertussis-derived palmitic acid (PA) as a crucial pro-inflammatory mediator that promotes MT28 pathogenicity via the TLR4/NF-κB signaling pathway. These findings elucidate the mechanisms underlying the prevalence and increased pathogenicity of the MT28 lineage, and propose a novel pathogenic mechanism of B. pertussis involving PA-mediated activation of the TLR4/NF-κB inflammatory signaling pathway.</p>

2025-06-21 | MTBLS12625 | MetaboLights

TLR4-NFkB-phospho-NF-kB signaling in BMDM

Project description:The model was constructed to describe TLR4 induced NF-κB activation in native bone marrow-derived macrophages. It included processes of ligand (lipopolysaccharide) recognition, formation of dimer receptor complex and further signal transduction through TRAF6/TAK1 complex that leads to the activation of IKKα/β kinase, which in turn enables the NF-κB transcription factor phosphorylation and translocation in the cell nucleus, and induction of IkB and WIP1 (as an example of induced protein that promotes NF-κB dephosphorylation 2) gene transcription. Models were based on the current knowledge of TLR signaling framework, protein interactions within the TLR4 pathway, and up-to-date mathematical models describing Toll receptor activation. The major important additions were made to TLR4 signaling description: 1) Receptor dimerization process 2) The existence of a basal nuclear NF-κB level (translocation) 3) NF-κB phosphorylation by IKK complex

2019-03-27 | MODEL1809230001 | BioModels

TLR4/NF-κB-responsive microRNAs in a mouse model of skeletal muscle ischemia-reperfusion injury

Project description:TLR4/NF-κB signaling plays a central mediator in response to danger signals released in the muscle ischemia-reperfusion injury (IRI). This study was designed to profile TLR4/NF-κB-responsive microRNAs (miRNAs) in the skeletal muscles following IRI. Following 2 h of ischemia and subsequent reperfusion for indicated times (0 h, 4 h, 1 d, and 7 d) of the isolated thigh skeletal muscles based on femoral artery perfusion of C57BL/6, Tlr4–/–, and NF-κB–/–mice, the muscle specimens were analyzed with an miRNA array to detect the TLR4/NF-κB-responsive miRNAs.

2016-01-01 | GSE47730 | GEO

Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling: HP scRNA-seq

Project description:RUNX1 is frequently mutated in myeloid and lymphoid malignancies. It has been shown to negatively regulate Toll-like receptor 4 (TLR4) signaling through nuclear factor kappa-B (NF-κB) in lung epithelial cells. Here we show that RUNX1 regulates TLR1/2 and TLR4 signaling and inflammatory cytokine production by neutrophils. Hematopoietic-specific RUNX1 loss increased the production of pro-inflammatory mediators, including tumor necrosis factor α (TNF-α), by bone marrow (BM) neutrophils in response to TLR1/2 and TLR4 agonists. Hematopoietic RUNX1 loss also resulted in profound damage to the lung parenchyma following inhalation of the TLR4 ligand lipopolysaccharide (LPS). However, neutrophils with neutrophil-specific RUNX1 loss lacked the inflammatory phenotype caused by pan-hematopoietic RUNX1 loss, indicating that dysregulated TLR4 signaling is not due to loss of RUNX1 in neutrophils per se, and single cell RNA sequencing indicates the dysregulation originates in a neutrophil precursor. Enhanced inflammatory cytokine production by neutrophils following pan-hematopoietic RUNX1 loss correlated with increased degradation of the inhibitor of NF-κB signaling (IκBα), and RUNX1-deficient neutrophils displayed broad transcriptional upregulation of many of the core components of the TLR4 signaling pathway. Hence early, pan-hematopoietic RUNX1 loss de-represses an innate immune signaling transcriptional program that is maintained in terminally differentiated neutrophils, resulting in their hyper-inflammatory state. We hypothesize that inflammatory cytokine production by neutrophils may contribute to leukemia associated with inherited RUNX1 mutations.

2020-02-17 | GSE144482 | GEO

Runx1 negatively regulates inflammatory cytokine production by neutrophils in response to Toll-like receptor signaling: PMN bulk RNA-seq

2020-02-17 | GSE144481 | GEO

Interactome profiling of a lysine deacetylase trapping probe library uncovers crosstalk between HDAC6 and NF-κB signaling

Project description:Lysine or histone deacetylases (HDACs) remove acetyl groups from lysine residues of numerous proteins, thereby regulating their function, activity and localization. Putative HDAC6 substrate sites, uncovered in the acetylome of HDAC6 knockdown cells, served as basis for the design of an HDAC6-trapping peptide library containing hydroxamic acids. Most probes enriched HDAC6 stronger from cell lysates than HDAC1. Probe sequences derived from α-tubulin, CRTC3, HSP90 and PPIA were confirmed as HDAC6 substrates and proteomics profiling of the corresponding trapping probes revealed preferential enrichment of HDAC6 together with known and previously unknown binding proteins. These included proteins of the NF-κB signaling complex which were independently confirmed as HDAC6 binders. NF-κB protein p50 was deacetylated by HDAC6 counteracting enhanced transcription of NF-κB target genes induced by p50 acetylation. These findings indicate a potential anti-inflammatory function of HDAC6 in NF-κB signaling.

2025-07-02 | PXD044143 | JPOST Repository

effect of chinese madicine on plasma exosomal proteins in Primary Sjogren's syndrome

Project description:Modified Zengye Decoction, a traditional chinese medicine, can effectively alleviate SS symptoms, while its mechanism may be associated with the reduced protein expression in insulin response, porphyrin and chlorophyll metabolism, and the TLR4/NF-κB pathway.

2022-10-15 | PXD033627 | Pride

A pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics

Project description:Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. RNA profiles of wild type (WT) MEFs treated with TNF-alpha were generated by deep sequencing using Illumina GAIIx. Examination of H3K4me3 histome modification in MEF.

2013-08-05 | E-GEOD-47494 | biostudies-arrayexpress

LPS-induced TIR domain complex acetylation activated TLR4/MAL/MyD88 signal pathway in sepsis

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 | PXD052433 | Pride

LncRNA Gm26917 promotes macrophage differentiation by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury

Project description:Our studies demonstrated that Gm26917 localized in the cytoplasm of hepatic macrophages and globally regulated expressions of inflammatory genes and differentiation of macrophages. In vivo study showed that lentivirus-mediated gene silencing of Gm26917 attenuated liver inflammation and protected mice from LPS-induced ALI. Furthermore, mechanistic study showed that 3’- truncation of Gm26917 interacts with N-terminus of Annexin A1, a negative regulator of NF-κB signaling pathway. We also found that Gm26917 knockdown suppressed NF-κB activity by decreasing the ubiquitination of Annexin A1 and its interaction with NEMO. Besides, expression of Gm26917 in inflammatory macrophage was regulated by transcription factor forkhead box M1 (FOXM1). LPS treatment could dramatically increase the binding of FOXM1 to the promoter region of Gm26917 in macrophages. In sum, our findings suggest that lncRNA Gm26917 silencing protected against LPS-induced liver injury by regulating TLR4/NF-κB signaling pathway in macrophages.

2022-09-01 | GSE185716 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data