Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TNF-R1 Co-opts TLR4 Pathway Components CD14, TRAM and TRIF to Drive TNF-Induced Inflammation and Toxicity

ABSTRACT: We report the application of single-cell-sequencing technology for the profiling of TRIF-dependent changes in immune cell populations, and TRIF-dependent cellular responses in the spleens of mice 4 hours after intravenous injection with recombinant murine TNF.

ORGANISM(S): Mus musculus

PROVIDER: GSE211539 | GEO | 2022/08/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TNF-R1 Co-opts TLR4 Pathway Components CD14, TRAM and TRIF to Drive TNF-Induced Inflammation and Toxicity

Project description:TNF-R1 Co-opts TLR4 Pathway Components CD14, TRAM and TRIF to Drive TNF-Induced Inflammation and Toxicity

| PRJNA870769 | ENA

Neutrophils and macrophages drive TNF-induced lethality via TRIF/CD14-mediated responses.

Project description:TNF mediates a variety of biological processes including cellular proliferation, inflammatory responses, and cell death and is therefore associated with numerous pathologies including autoinflammatory diseases and septic shock. The inflammatory and cell death responses to TNF have been studied extensively downstream of TNF-R1 and are believed to rely on the formation of proinflammatory complex I and prodeath complex II, respectively. We recently identified a similar multimeric complex downstream of TLR4, termed the TRIFosome, that regulates inflammation and cell death in response to LPS or Yersinia pseudotuberculosis. We present evidence of a role for the TRIFosome downstream of TNF-R1, independent of TLR3 or TLR4 engagement. Specifically, TNF-induced cell death and inflammation in murine macrophages were driven by the TLR4 adaptor TRIF and the LPS co-receptor CD14, highlighting an important role for these proteins beyond TLR-mediated immune responses. Via immunoprecipitation and visualization of TRIF-specific puncta, we demonstrated TRIF- and CD14-dependent formation of prodeath and proinflammatory complexes in response to TNF. Extending these findings, in a murine TNF-induced sepsis model, TRIF and CD14 deficiency decreased systemic inflammation, reduced organ pathology, and improved survival. The outcome of TRIF activation was cell specific, because TNF-induced lethality was mediated by neutrophils and macrophages responding to TNF in a TRIF-dependent manner. Our findings suggest that in addition to their crucial role in TNF production, myeloid cells are central to TNF toxicity and position TRIF and CD14 as universal components of receptor-mediated immune responses.

| S-EPMC10021564 | biostudies-literature

In vitro responses of PBMC and fibroblasts from patients with TRIF deficiency after TRIF dependent and independent stimuli

2011-10-20 | GSE32390 | GEO

In vitro responses of PBMC and fibroblasts from patients with TRIF deficiency after TRIF dependent and independent stimuli

Project description:We report here unrelated HSE patients with autosomal recessive (AR) or autosomal dominant (AD) TRIF deficiency. The AR form of the disease is due to a homozygous nonsense mutation, resulting in a complete absence of the TRIF protein. Both the TLR3 and the TRIF-dependent TLR4 signaling pathways are abolished. The AD form of TRIF deficiency is due to a heterozygous missense mutation resulting in a dysfunctional protein. The TLR3 signaling pathway is impaired, whereas the TRIF-dependent TLR4 pathway is unaffected. Both patients however showed reduced capacity to respond to cytosolic double stranded RNA, consistent with recent reports of TRIF’s involvement in the DExD/H-box helicases pathway. Skin fibroblast cell lines were derived from healthy controls (n=3), patient with deficiencies for TRIF (n=1), MYD88 (n=1), and TLR3 (n=1) and cultured for 4 hours in the presence of IL1B (20ng/ml) or poly I:C (25ng/ml) or left unstimulated for the same length of time. PBMCs (previously frozen) collected from a healthy control (n=1) and patients with deficiencies for TRIF (n=1), and MYD88 (n=1) were cultured together with LPS (10ng/ml) or R848 (3ug/ml) for 2hrs or left unstimulated for the same length of time.

2011-10-19 | E-GEOD-32390 | biostudies-arrayexpress

Transcription profiling of mouse spleen after immunized using LPS vs MPL as adjuvant.

Project description:An unresolved issue in immunology is the extent to which inflammatory effects are needed for robust T cell responses. In this study, mice were immunized by iv injection using either high toxicity lipopolysaccharide (LPS) or low toxicity monophosphoryl lipid A (MPL) as adjuvant. Six hours after iv immunization, whole spleens were harvested and gene expression was measured in unfractionated splenic populations of cells. The analysis indicated that the low toxicity adjuvanticity of MPL was associated with TLR4-mediated signaling that was biased to the TRIF branch of TLR4, while LPS generated balanced MyD88 and TRIF-associated outcomes. Experiment Overall Design: B6.SJL mice adoptively transferred with T cells from B6.OTI and OTII transgenic TCR transgenic were immunized via intravenous injection with ova peptides alone ("Ova"), or with LPS ("OvaLPS") or MPL as adjuvant ("OvaMPL"). Six hours after immunization, the mice were euthanized by cervical dislocation, the spleens were removed and immediately lysed in guanidium chloride, and kept frozen until being used to extract total cellular RNA. Three mice each were given the indicated treatments, with independent processing and analysis of nine samples total.

2008-06-15 | E-GEOD-7768 | biostudies-arrayexpress

Transcription profiling of mouse LPS-stimulated macrophages from wild-type, MyD88-/- and TRIF-/- animals

Project description:Lipopolysaccharide (LPS), a Toll-like receptor (TLR) 4 ligand, activates intracellular signaling via adaptors, MyD88 and TRIF, leading to the expression of various genes including proinflammatory cytokines. We used microarrays to examine influence of MyD88 or TRIF deficiency in LPS-inducible gene expression. Experiment Overall Design: Peritoneal macrophages from wild-type, MyD88-/- and TRIF-/- mice were stimulated with LPS for 0, 1 and 4 hours, followed by RNA extraction. Then hybridization on affymetrix microarrays was performed.

2009-03-01 | E-GEOD-14890 | biostudies-arrayexpress

Expression data of LPS-stimulated macrophages from wild-type, MyD88-/- and TRIF-/- mice.

2009-02-19 | GSE14890 | GEO

Myd88, Trif, and Rip2-independent macrophage responses to Legionella pneumophila

Project description:Microarray analysis of Myd88-/-Trif-/- and Myd88-/-Rip2-/- macrophage responses to WT or dotA mutant L. pneumophila. Keywords: Expression profiling by microarray

2008-11-15 | GSE13147 | GEO

TRIF drives homeostatic signalling in IECs

Project description:TRIF signalling drives homeostatic intestinal epithelial antimicrobial peptide expression

| PRJEB6686 | ENA

Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance

Project description:Macrophage deletion of Noc4l triggers endosomal TLR4/TRIF signal and leads to insulin resistance

| PRJNA593508 | ENA