Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microbial-ligand independent regulation of lymphpoiesis by NOD1

ABSTRACT: Aberrant differentiation of progenitor cells in the hematopoietic system is known to severely impact host immune responsiveness. Here we demonstrate that NOD1, a cytosolic innate sensor of bacterial peptidoglycan, also functions in murine hematopoietic cells as a major regulator of both the generation and differentiation of lymphoid progenitors as well as peripheral T lymphocyte homeostasis. We further show that NOD1 mediates these functions by facilitating STAT5 signaling downstream of hematopoietic cytokines. In steady-state, loss of NOD1 resulted in a modest but significant decrease in numbers of mature T, B and NK cells. During systemic protozoan infection, this defect was markedly enhanced leading to host mortality. Lack of functional NOD1 also impaired T-cell-dependent anti-tumor immunity while preventing colitis. These findings reveal that in addition to its classical role as a bacterial ligand receptor, NOD1 plays an important function in regulating adaptive immunity through interaction with a major host cytokine signaling pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE236485 | GEO | 2023/10/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Immune surveillance of cellular homeostasis by NOD1/2 via sensing cytosolic sphingosine-1-phosphate (S1P)

Project description:Chronic inflammation is associated with disruption of cellular homeostasis, yet the underlying mechanisms remain elusive1. Nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2) are intracellular pathogen recognition receptors that activate innate immune responses via sensing bacterial peptidoglycans2-4. We demonstrate that NOD1/2 sense not only microbe-specific molecular patterns but also perturbation of cell homeostasis, and thereby cause inflammation. Host generation of sphingosine-1-phosphate (S1P) via the hydrolysis pathway is essential for NOD1/2 signaling upon such stress. Cytosolic delivery of S1P activates NOD1/2 dependent NF-κB activation and inflammation. Finally, we demonstrate that S1P directly binds to and activates NOD1/2. In sum, we describe a hitherto unknown role of NOD1/2 by revealing that they initiate innate immune responses by surveillance of cellular homeostasis through sensing of cytosolic S1P. Our findings provide a novel link between host cytosolic S1P and NOD1/2 mediated immune activation upon perturbation of cellular homeostasis and thus form the basis for future intervention strategies targeting the S1P-NOD1/2 axis.

2020-01-01 | GSE124828 | GEO

Zebrafish embryos microinjected with ptGFP1 (control group) or ptGFP1-NOD1 (NOD1 group)

Project description:Transcriptional profiling of zebrafish embryos comparing control group microinjected with empty plasmid with NOD1 group microinjected with ptGFP1-NOD1 plasmid.

2018-06-22 | GSE116109 | GEO

Nod1-dependent NF-kB activation initiates hematopoietic stem cell specification in response to small Rho GTPases

Project description:The possibility of specifying functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (hPSCs) would overcome current limitations related to HSPC transplantation. However, generating hPSC-derived HSPCs has been elusive, necessitating a better understanding of the native developmental mechanisms that trigger HSPC specification. Here, we revealed in vivo an intrinsic inflammatory mechanism triggered by Nod1 that drives early hemogenic endothelium (HE) patterning to specify HSPCs. Our genetic and chemical experiments showed that HSPCs failed to specify in the absence of Nod1 and its downstream kinase Ripk2. Rescue experiments demonstrated that Nod1 and Ripk2 acted through NF-kB, and that small Rho GTPases are at the apex of this mechanism. Manipulation of NOD1 in a human system of hPSCs differentiation towards the definitive hematopoietic lineage indicated functional conservation. This work establishes the RAC1-NOD1-RIPK2-NFkB axis as the earliest inflammatory inductor that intrinsically primes the HE for proper HSPC specification. Manipulation of this pathway could help derive a competent HE amenable to specify functional patient specific HSPCs for the treatment of blood disorders. Keywords: NOD1, RIPK2, NF-kB, RAC1, Rho GTPases, Hematopoietic Stem and Progenitor Cell Specification, Hemogenic Endothelium.

2023-10-26 | GSE224708 | GEO

NLR Nod1 signaling promotes survival of BCR-engaged mature B cells through upregulated Nod1 as a positive outcome

Project description:BCR ligand-engaged B cells upregulate Nod1 during development. Most mature B cells have up-regulated Nod1 and are sensitive to Nod1 signaling, which increases survival upon exposure to microbial products, as a positive outcome of BCR-engaged mature B cells.

2017-09-03 | GSE101318 | GEO

Expression analysis of Arabidopsis peptidoglycan (PGN) recognition mutants treated with PGN

Project description:Recognition of microbial patterns by host pattern recognition receptors is a key step in immune activation in multicellular eukaryotes. Peptidoglycans (PGN) are major components of bacterial cell walls and possess immunity-stimulating activities in metazoans and plants. Here, we show that PGN sensing in Arabidopsis thaliana requires three LysM domain proteins, LYM1, LYM3 and CERK1. A 24 DNA microarray study using toral RNA from three Arabidopsis mutants (lym1-1, lym3-1, cerk1-2) as well as wild type treated with water or peptidoglycan.

2011-11-10 | E-GEOD-28004 | biostudies-arrayexpress

A modest change in regulation of NOD1 expression has a major impact on inflammation and gastric cancer

Project description:Altered protein dosage by defects in single genes leads to haploinsufficiencies and monogenic disorders, but the impact of small changes in gene expression on multifactorial disease is unknown. Here we show that a persistent small increase in expression of NOD1, a key innate sensor of bacterial infection, precipitates a large physiological effect with dramatically altered cellular function associated with carcinogenesis. Inhibition of miR-15b and miR-16 microRNA function leads to a ~1.2-1.4 fold increase in NOD1 protein concentration, with even slightly greater increases leading to ligand-independent, switch-like NOD1 activation. miRNA regulation of NOD1 is impaired in gastric cancer with a small increase being associated with greater early disease mortality. Overall, our data show that tight control of NOD1 expression by miRNA prevents this sensor from exceeding a physiological switching checkpoint that promotes persistent inflammation and lethal cancer progression, and reveal the impact of a single and modest cellular alteration on cancer.

2020-10-01 | GSE99550 | GEO

METTL3 Regulates LPS-Induced Inflammatory Response via the NOD1 Signaling Pathway

Project description:Inflammation is normally a protective response to defend and restore homeostasis; nonresolving inflammation is a major driver of immune disorders. N6-methyladenosine (m6A) is a prevalent mRNA modification that plays a crucial function in multiple biological processes. The effect of m6A on the immune response has recently been reported. However, the effect is unclear, and the results are contradictory. In this study, the expression of total m6A and the methyltransferase METTL3 decreased in LPS-stimulated macrophages. METTL3 knockdown significantly upregulated expression of proinflammatory cytokines, including TNF-α, IL-6 and NO. RNA sequencing analysis showed that the upregulated genes were enriched in inflammation-related signaling pathways and that the NOD-like receptor signaling pathway might be the target molecules of METTL3. METTL3 depletion resulted in upregulation of the NOD1 pathway without impacting NOD2. Moreover, the increase in proinflammatory cytokines induced by METTL3 knockdown was reversed by blocking the NOD1 pathway using the NOD-IN-1 and ML130 specific inhibitors. Mechanistically, METTL3 knockdown promoted the mRNA expression and stability of NOD1 and RIPK2, and the same results were detected in m6A-binding protein YTHDF1- or YTHDF2-silenced cells. All findings suggested that METTL3 depletion inhibits the degradation of NOD1 and RIPK2 mRNA mediated by YTHDF1 and YTHDF2, which upregulate the NOD1 pathway and subsequently promote the LPS-induced inflammatory response in macrophages.

2022-06-01 | GSE189412 | GEO

Microbial-ligand independent regulation of lymphpoiesis by NOD1

Project description:Microbial-ligand independent regulation of lymphpoiesis by NOD1

| PRJNA991463 | ENA

Zebrafish embryos microinjected with ptGFP1 (control group) or ptGFP1-NOD1 (NOD1 group)

Project description:Zebrafish embryos microinjected with ptGFP1 (control group) or ptGFP1-NOD1 (NOD1 group)

| PRJNA477292 | ENA

Peptidoglycan metabolite photoaffinity reporters reveal direct binding to intracellular pattern recognition receptors and Arf GTPases

Project description:Extensive structure-activity studies of iE-DAP and MDP have demonstrated their selective activation of NOD1- and NOD2-expressing cells, respectively. Nonetheless, the direct binding of iE-DAP and MDP to NOD1 and NOD2, respectively, as well as other proteins in mammalian cells has not been systematically investigated. To address the direct interaction of iE-DAP and MDP with NOD1 and NOD2 in living cells, we synthesized a series of peptidoglycan metabolite photoaffinity chemical reporters containing a diazirine for photocrosslinking in cells and an alkyne tag for bioorthogonal detection of covalently-labeled proteins. The analysis of these peptidoglycan metabolite photoaffinity reporters demonstrate that iE-DAP and MDP can directly bind to NOD1 and NOD2 in mammalian cells. The crosslinking of these peptidoglycan metabolite photoaffinity reporters only occur with active variants of NOD1 and NOD2. Beyond direct binding to NOD2, the active MDP photoaffinity reporter selectively crosslinked Arf GTPases in NOD2-expressing cells and did so most prominently with GTP-bound Arf6, revealing the Arf proteins as novel direct pattern recognition receptors. Additional labeling and co-precipitation experiments suggest that MDP induces a complex between NOD2 and GTP-Arf6. This study highlights the utility of peptidoglycan metabolite photoaffinity reporters for characterizing their direct binding to intracellular pattern recognition receptors and identifying unpredicted cellular cofactors. The applications of these microbial-specific metabolite reporters should enable the discovery of other receptors, transporters and regulatory enzymes in host cells and microbes.

2020-05-26 | PXD012350 | Pride

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