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O6-Methylguanine DNA Methyltransferase Regulates Beta-glucan Trained Immunity of Macrophages

ABSTRACT: O6-Methylguanine DNA Methyltransferase Regulates Beta-glucan Trained Immunity of Macrophages

PROVIDER: PRJNA965794 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24386229_1.fastq.gz	Fastqsanger.gz
	SRR24386229_2.fastq.gz	Fastqsanger.gz
	SRR24386230_1.fastq.gz	Fastqsanger.gz
	SRR24386230_2.fastq.gz	Fastqsanger.gz
	SRR24386231_1.fastq.gz	Fastqsanger.gz

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O6-Methylguanine DNA Methyltransferase Regulates Beta-glucan Trained Immunity of Macrophages

Project description:Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by β-glucan (BG). Pharmacological inhibition or silencing of MGMT expression altered LPS stimulated pro-inflammatory cytokine productions in BG-trained bone marrow derived macrophages (BMMs). Targeted deletion of Mgmt in BMMs resulted in reduction of the trained responses both in vitro and in vivo models. The transcriptomic analysis revealed that the dampening trained immunity in MGMT KO BMMs is partially mediated by ATM/FXR/AMPK axis affecting the MAPK/mTOR/HIF1α pathways and the reduction in glycolysis function. Taken together, a failure to resolve a DNA damage may have consequences for innate immune memory.

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The effect of beta-glucan - induced trained immunity on the transcriptomic profile of bone marrow granulocyte-macrophage progenitors (GMP)

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Project description:Induction of trained immunity by beta-glucan affects myeloid cells and their bone marrow progenitors. In particular, broad epigenetic alterations in trained myeloid cells have been demonstrated. In this study, we performed single cell ATAC sequencing in GMP and neutrophils from beta-glucan treated mice, as compared to control-treated mice, in order to investigate the impact of trained immunity on the epigenetic profile of GMP and neutrophils.

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