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Series GSE102677 Query DataSets for GSE102677
Status Public on Jun 16, 2019
Title Metformin alters human host responses to Mycobacterium tuberculosis in-vitro and in healthy human subjects [PBMC RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Metformin, the most widely administered diabetes drug, has been proposed as a candidate for host directed therapy for tuberculosis although very little is known about its effects on human host responses to Mycobacterium tuberculosis. When added in vitro to PBMCs isolated from healthy non-diabetic volunteers, metformin increased glycolysis, inhibited the mTOR targets, strongly reduced M. tuberculosis induced production of TNF-alpha (-58%), IFN-gamma (-47%) and IL-beta (-20%), while increasing phagocytosis. In healthy subjects, in vivo metformin intake induced significant transcriptional changes in whole blood and isolated PBMCs, with substantial down-regulation of genes related to inflammation and the type 1 interferon response. Metformin intake also increased monocyte phagocytosis (by 1.5 to 2 fold) and ROS production (+20%). These results show that metformin in humans has a range of potentially beneficial effects on cellular metabolism, immune function and gene-transcriptional level, that affect innate host responses to M. tuberculosis. This underlines the importance of cellular metabolism for host immunity and supports a role for metformin as host-directed therapy for tuberculosis.
Overall design Peripheral Mononuclear Cells taken from 11 healthy donors, prior to administration of metformin and after 5 days of metformin. Samples were stimulated with Mycobacterium tuberculosis lysate or cultured unstimulated for 4 hours. Total 88 samples, with 11 clinical replicates.
Contributor(s) Cliff JM, Eckold C, Lachmandas E, Dockrell HM, Netea MG, van Crevel R
Citation(s) 30753544
Submission date Aug 15, 2017
Last update date Jun 18, 2019
Contact name Jackie Cliff
Organization name London School of Hygiene & Tropical Medicine
Department Immunology and Infection
Street address Keppel Street
City London
ZIP/Postal code WC1E 7HT
Country United Kingdom
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (44)
GSM2742763 Baseline_patient_1_Unstim
GSM2742764 Baseline_patient_1_Mtb
GSM2742765 Metformin_patient_1_Unstim
This SubSeries is part of SuperSeries:
GSE102678 Metformin alters human host responses to Mycobacterium tuberculosis in-vitro and in healthy human subjects
BioProject PRJNA398377
SRA SRP115480

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Supplementary file Size Download File type/resource
GSE102677_RAW.tar 8.8 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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