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Expression profile of Human blood monocytes treated with bacterial lipids

ABSTRACT: Expression profile of Human blood monocytes treated with bacterial lipids

PROVIDER: PRJNA819457 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18795400_1.fastq.gz	Fastqsanger.gz
	SRR18795400_2.fastq.gz	Fastqsanger.gz
	SRR18795401_1.fastq.gz	Fastqsanger.gz
	SRR18795401_2.fastq.gz	Fastqsanger.gz
	SRR18795402_1.fastq.gz	Fastqsanger.gz

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Expression profile of Human blood monocytes treated with bacterial lipids

Project description:Multiple studies have established associations between human gut bacteria and host physiology but determining the molecular mechanisms underlying these associations has been challenging1–3. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favorable outcomes to checkpoint blockade in cancer immunotherapy, and homeostatic immunity4–7. Here we report the identification of a lipid from A. muciniphila’s cell membrane that recapitulates the immunomodulatory activity of A. muciniphila in cell-based assays8. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure-activity relationship, and its immune signaling requires an unexpected toll-like receptor 2/1 heterodimer9,10. Certain features of the phospholipid’s activity are noteworthy: it is significantly less potent than known natural and synthetic toll-like receptor 2 agonists; it preferentially induces some inflammatory cytokines but not others; and at low doses (1% of EC50) it resets activation thresholds and responses for immune signaling. Identifying both the molecule and an equipotent synthetic analog, its non-canonical toll-like receptor 2/1 signaling pathway, its immunomodulatory selectivity, and its low dose immunoregulatory effects provides a molecular mechanism for a model of A. muciniphila’s ability to set immunological tone and its varied roles in health and disease.

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Project description:Total mRNA expression of CXCL12-treated monocytes was compared with control untreated monocytes Human Peripheral blood monocytes from three different healthy donors were isolated by anti-CD14-labeled magnetic microbeads. CD14+ monocytes were cultured in teflon dishes for 1h in RPMI 10% FCS and then, were treated or not with CXCL12 for 6h. Total RNA from each condition was extracted and purified using the RNasey kit (Qiagen). Labelled RNA was used as hybridization probes on human Codelink Whole genome Bioarray. All experimental procedures were performed following manufacturer instructions. Microarrays were scanned with a GenePix 4000B (Axon Instruments) scanner. Scanned images and raw data were processed using the Codelink Expression Software.

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