Dataset Information

Priming conditions alter the proteome near the PVM

ABSTRACT: investigate the proximal proteins on the porositophorous vacuole membranes when toxoplasma gondii ME49 infected mouse bone marrow derived dendritic cells were primed under different conditions. The priming condition using IFN gamma will induce the formation of GBP+ puncta on a portion of PVM. The constituents of the GBP+ puncta are also investigated.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Dendritic Cell, Cell Culture

DISEASE(S): Toxoplasmosis

SUBMITTER: BOCHENG YIN

LAB HEAD: Sarah E. Ewald

PROVIDER: PXD027716 | Pride | 2024-02-14

REPOSITORIES: Pride

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Publications

Inducible nitric oxide synthase (iNOS) is necessary for GBP-mediated T. gondii restriction in murine macrophages via vacuole nitration and intravacuolar network collapse.

Zhao Xiao-Yu XY Lempke Samantha L SL Urbán Arroyo Jan C JC Yin Bocheng B Holness Nadia K NK Smiley Jamison J Ewald Sarah E SE

bioRxiv : the preprint server for biology 20230725

Toxoplasma gondii is an obligate intracellular, protozoan pathogen of rodents and humans. T. gondii's ability to grow within cells and evade cell-autonomous immunity depends on the integrity of the parasitophorous vacuole (PV). Interferon-inducible guanylate binding proteins (GBPs) are central mediators of T. gondii clearance, however, the precise mechanism linking GBP recruitment to the PV and T. gondii restriction is not clear. This knowledge gap is linked to hetero ...[more]

PMID: 37546987

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Project description:Ineffective hematopoiesis is a hallmark of myelodysplastic syndromes (MDS). Hematopoietic alterations in MDS patients strictly correlate with microenvironment dysfunctions, eventually affecting also the mesenchymal stromal cells (MSCs) compartment. Stromal cells are indeed epigenetically reprogrammed to cooperate with leukemic cells and propagate the disease as "tumor unit"; therefore, changes on MSCs epigenetic profile might contribute to the hematopoietic perturbations typical of MDS. Here, we unveil that the histone variant macroH2A1 (mH2A1) regulates the crosstalk between epigenetics and inflammation in MDS-MSCs, potentially affecting their hematopoietic support ability. We show that the mH2A1 splicing isoform mH2A1.1 accumulates in MDS-MSCs, correlating with the expression of the Toll-like receptor 4 (TLR4), an important pro-tumor activator of MSC phenotype associated to a pro-inflammatory behavior. MH2A1.1-TLR4 axis was further investigated in HS-5 stromal cells after ectopic mH2A1.1 overexpression (mH2A1.1-OE). Proteomic data confirmed the activation of a pro-inflammatory signature associated to TLR4 and nuclear factor kappa B (NFkB) activation. Moreover, mH2A1.1-OE proteomic profile identified several upregulated proteins associated to DNA and histones hypermethylation, including S-adenosylhomocysteine hydrolase, a strong inhibitor of DNA methyltransferase and of the methyl donor S-adenosyl-methionine (SAM). HPLC analysis confirmed higher SAM/SAH ratio along with a metabolic reprogramming. Interestingly, an increased LDHA nuclear localization was detected both in mH2A1.1-OE cells and MDS-MSCs, probably depending on MSC inflammatory phenotype. Finally, coculturing healthy mH2A1-OE MSCs with CD34+ cells, we found a significant reduction in the number of CD34+ cells, which was reflected in a decreased number of colony forming units (CFU -Cs). These results suggest a key role of mH2A1.1 in driving the crosstalk between epigenetic signaling, inflammation and cell metabolism networks in MDS-MSCs.

Dataset Information

Priming conditions alter the proteome near the PVM

Publications

Inducible nitric oxide synthase (iNOS) is necessary for GBP-mediated <i>T. gondii</i> restriction in murine macrophages via vacuole nitration and intravacuolar network collapse.

Similar Datasets

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