PLX084779

GSE102633: Metformin alters human host responses to Mycobacterium tuberculosis in-vitro and in healthy human subjects [Ex vivo Blood RNA-Seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

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- (-58%), IFN-gamma (-47%) and IL-1 (-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. SOURCE: Jackie Cliff (jackie.cliff@lshtm.ac.uk) - London School of Hygiene & Tropical Medicine