Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/149037
Title: Metformin alters human host responses to Mycobacterium tuberculosis in healthy subjects
Authors: Lachmandas, Ekta
Eckold, Clare
Böhme, Julia
Koeken, Valerie A. C. M.
Mardiana Marzuki
Blok, Bastiaan
Arts, Rob J. W.
Chen, Jinmiao
Teng, Karen W. W.
Ratter, Jacqueline
Smolders, Elise J.
Van den Heuvel, Corina
Stienstra, Rinke
Dockrell, Hazel M.
Newell, Evan
Netea, Mihai G.
Singhal, Amit
Cliff, Jacqueline M.
Van Crevel, Reinout
Keywords: Science::Medicine
Issue Date: 2019
Source: Lachmandas, E., Eckold, C., Böhme, J., Koeken, V. A. C. M., Mardiana Marzuki, Blok, B., Arts, R. J. W., Chen, J., Teng, K. W. W., Ratter, J., Smolders, E. J., Van den Heuvel, C., Stienstra, R., Dockrell, H. M., Newell, E., Netea, M. G., Singhal, A., Cliff, J. M. & Van Crevel, R. (2019). Metformin alters human host responses to Mycobacterium tuberculosis in healthy subjects. Journal of Infectious Diseases, 220(1), 139-150. https://dx.doi.org/10.1093/infdis/jiz064
Project: 15302FG151
Journal: Journal of Infectious Diseases
Abstract: Background" Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. Methods: We investigated in vitro and in vivo effects of metformin in humans. Results: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. Conclusion: Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis.
URI: https://hdl.handle.net/10356/149037
ISSN: 0022-1899
DOI: 10.1093/infdis/jiz064
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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